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Original Article

Anat Cell Biol 2020; 53(3): 272-278

Published online September 30, 2020


Copyright © Korean Association of ANATOMISTS.

Incidence of hypoplastic posterior communicating artery and fetal posterior cerebral artery in Andhra population of India: a retrospective 3-Tesla magnetic resonance angiographic study

Sharmila P Bhanu1 , Suneetha Pentyala2 , Devi K Sankar1

1Department of of Anatomy, Narayana Medical College, Nellore, Andhra Pradesh, 2Department of of Radiology, Narayana Medical College & General Hospital, Nellore, Andhra Pradesh, India

Correspondence to:Devi K Sankar
Department of of Anatomy, Narayana Medical College, Chinthareddypalem, Nellore, Andhra Pradesh 524003, India
E-mail: lesanshar@gmail.com

Received: March 20, 2020; Revised: May 16, 2020; Accepted: May 21, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

The posterior communicating arteries (PCoA) are important component of collateral circulation between the anterior and posterior part of circle of Willis (CW). The hypoplasia or aplasia of PCoA will reflect on prognosis of the neurological diseases. Precise studies of the incidence of hypoplastic PCoA in Andhra Pradesh population of India are hitherto unreported, since the present study was undertaken. Two hundred and thirty one magnetic resonance angiography (MRA) images were analyzed to identify the hypoplasia of PCoA and presence of fetal type of posterior cerebral artery (f-PCA) in patients with different neurological symptoms. All the patients underwent 3.0T MRI exposure. The results were statistically analysed. A total of 63 (27.3%) PCoA hypoplasia and 13 cases with f-PCA (5.6%) cases were identified. The hypoplastic PCoA was noted more in males than females (P<0.05) and right side hypoplasia was common than the left (P<0.04); bilateral hypoplasia of PCoA was seen in 37 cases out of 63 and is significant. The hypoplastic cases of the present study also were associated with variations of anterior cerebral arteries and one case was having vertebral artery hypoplasia. Incidence of PCoA as unilateral or bilateral with other associated anomalies of CW is more prone to develop stroke, migraine and cognitive dysfunction. Knowledge of these variations in the PCoA plays a pivotal role in diagnoses of neurological disorders and in neurovascular surgeries and angiographic point of view.

Keywords: Posterior communicating artery, Hypoplastic, Posterior cerebral artery, Circle of Willis, Cerebral artery

Detailed anatomy of the circle of Willis (CW) or circulus arteriosus is important in the field of neurology, neurosurgery and anatomy. The CW is the main arterial structure located at base of the brain that establishes collateral circulation to the brain and surrounding structures. The arterial circle is formed by internal carotid and vertebro-basilar systems comprising anterior cerebral artery (ACA), proximal segments of internal carotid and proximal segments of posterior cerebral arteries from basilar artery. The CW normally equalizes the blood flow to various parts of the brain. But a complete CW is seen in minority of the population and as age advances it shows different types of anatomical variations in its branches since birth [1].

Posterior communicating artery (PCoA), branch of internal carotid artery acts as a significant anastomotic channel between anterior and posterior cerebral circulations [2]. Each PCoA runs postero-medially and anastomose at the junction between pre (P1) and post-communicating (P2) segments of ipsilateral posterior cerebral artery (PCA) [3]. The PCoA occasionally continues as PCA, called as fetal PCA (f-PCA) with a complete absence of P1 segment [4]. Its occurrence may be unilateral or bilateral, and in these conditions, the PCoA is bigger than the normal [5].

The PCoA establishes the collateral circulation through its penetrating branches which supply the ventrolateral and dorsomedial thalamic nuclei, tuber cinereum, mamillary bodies, and cerebral peduncles [6]. The PCoA hypoplasia and aplasia can be congenital variations characterized by a narrow or poorly developed artery with limited blood flow [1]. As PCoA render a vital communication between internal carotid and vertebro-basilar system, occlusion, aplasia or hypoplasia of this artery can significantly affect the vascularity of brain. In bilateral aplasia or hypoplasia, there will be a bilateral interruption of blood supply to the cerebellum. These anatomical variations reduce the accessibility of collateral vessels and its circulation. Hence identification of such variations is important in the evaluation of cerebral vascular morbidity and its allied treatments. The objective of the present study is to observe the variations in the arrangement of PCoA of CW.

The present study was a retrospective analysis of magnetic resonance angiography (MRA) of CW on 231 patients, which included 154 males and 77 females. The age of the patients with hypoplastic PCoA was minimum of 25 years and maximum of 79 years. The study was approved by the institutional ethical committee and clinical variables were abstracted from Institutional Neurology review board. The cases were obtained between the years 2016–2019 from the patients who had evidence of cerebral ischemic stroke (CIS), history of severe migraine, less hearing sense, dim vision and mild focal neurological deficit.

A time of flight (TOF)-MRA technique was used and the study was conducted and analyzed in the departments of radiology, anatomy, and neurology. All the patients underwent 3D TOF-MRA using 3.0T MRI machine (3.0T system, GE Discovery MR750w 3.0Tesla; GE Healthcare, Milwaukee, WI, USA) and imaging parameters used were (1) repetition time was 30 milliseconds and echo time was 2.7–3.1 milliseconds, (2) flip angle was 20°, (3) 200 mm field of view, (4) section thickness was 1.4 mm, and (5) the imaging time was approximately 4.49 minutes. The images obtained were processed using a maximum intensity projection algorithm to create an angiogram like image [7]. The reconstructed images were then analyzed to detect the hypoplastic (<1 mm in diameter) or aplastic PCoA and with or without the f-PCA. The PCoA with aneurysms were excluded from the study. Other than hypoplasia of PCoA, anomalies such as hypoplasia or aplasia of other cerebral arteries and its branches were also noted. The data obtained were analyzed with Statistical Package for Social Sciences software (IBM SPSS Statistics for Windows, Version 25.0. IBM Corp., Armonk, NY, USA). The statistical dependencies between age, side and sex were measured using the Student t-test. The differences between the male and female PCoA hypoplasia were assessed in relation to side using the Chi-square test. Probability values of P>0.05 were considered as statistically significant.

In the present study, out of 231 patients, 63 patients (27.3%) showed the incidence of hypoplastic PCoA in MRA pictures, which included 39 males (16.9%) and 24 females (10.4%). The mean age of males and females were 65.56±8.18 and 56.83±12.22 respectively (Table 1). The hypoplasia of PCoA was noted more in males than females (P<0.05). Out of 63 PCOA hypoplastic, unilateral cases included 26 of which right side PCoA hypoplasia (Fig. 1A) in males was 9 and in females 7 while the left side (Figs. 1B, 2A, 4B) was found to be 6 in males and 4 in females. The right sided hypoplasia was significant (P<0.04) than the left in the present study. The bilateral hypoplasia (Figs. 2B, 3A, 3B, 4A) was seen in 37 patients (58.7%), which included 24 males and 13 females and is found significant. Overall the statistical association between the hypoplasia of PCoA in relation to sex and side was found to be highly significant (P<0.001) (Table 2).

Table 1 . Independent sample-T and ANOVA tests to find the differences between the sex and side in patients with hypoplastic posterior communicating artery

VariableMale (in years)Female (in years)Totalt-valueP-value

Left side662.50±14.384579448.50±15.3529651056.90±15.671.4700.180a)
Right side969.00±6.636074755.29±17.3025741663.00±13.882.1970.045b)
Grand total3965.56±8.1845792456.83±12.2225756362.24±10.713.3990.001c)

N, number of cases observed; SD, standard deviation; Min, minimum; Max, maximum; t, results of independent sample t-test; P, difference between the sex, age and side & P<0.05 is considered significant; F and P are the results of ANOVA. a)Not significant; b)Significant; c)Highly significant

Table 2 . Cross-tabulation of side and sex-specific incidence of hypoplastic posterior communicating artery patients

SideNMaleFemaleTotalChi-square valueP-value
Left sideCount6410
% within left side60.0040.00100.00
% within sex15.3816.6715.87
Right sideCount9716
% within left side56.2543.75100.00
% within sex23.0829.1725.400.3690.831a)
% within left side64.8635.14100.00
% within sex61.5454.1758.73
Grand totalCount392463
% within left side61.9038.10100.00
% within sex100.00100.00100.00

N, number of cases observed. a)P-value by Chi-square test, not significant

Figure 1. MRA images showing (A) hypoplasia of right side PCoA (arrowhead) with left fetal type of posterior cerebral artery (arrow); (B) left side PCoA hypoplasia (arrowhead) with hypoplastic left A1 segment of anterior cerebral artery (asterisk). MRA, magnetic resonance angiography; PCoA, posterior communicating artery.
Figure 2. MRA images showing (A) left side PCoA hypoplasia (arrowhead); (B) bilateral PCoA hypoplasia (arrowheads). MRA, magnetic resonance angiography; PCoA, posterior communicating artery.
Figure 3. MRA images showing (A) bilateral PCoA hypoplasia (arrowheads); (B) bilateral PCoA hypoplasia (arrowheads) with hypoplastic A1 segment of anterior cerebral artery (asterisk). MRA, magnetic resonance angiography; PCoA, posterior communicating artery.
Figure 4. MRA images showing (A) bilateral PCoA hypoplasia (arrowheads) with hypoplastic right vertebral artery (arrow); (B) left side PCoA hypoplasia (arrowhead) with right fetal type of posterior cerebral artery (arrow); this case also presented hypoplastic right A1 segment of anterior cerebral artery (asterisk) and hypoplastic right vertebral artery (double arrows). MRA, magnetic resonance angiography; PCoA, posterior communicating artery.

The f-PCA was observed in 13 (5.6%) cases which is more on right (73.0%) (Fig. 4B) than left side (62.6%) (Fig. 1B) and the incidence is more or less equal in both males and females with no statistical significance (P<0.05) (Table 3).

Table 3 . Incidence of fetal PCA in relation to sex and side

VariablePresence of fetal PCA (N=13)

Male (n=154)3 (1.9%)3 (1.9%)1.0a)
Female (n=77)4 (5.2%)3 (3.9%)0.7a)
Chi-square value0.0660.7b)

PCA, posterior cerebral artery; N, number of fetal PCA cases observed; P, difference between the sex and side & P<0.05 is considered significant; n, total number of males or females. a)Not significant; b)P-value by Chi-square test, not significant; percentages are mentioned within brackets

Apart from hypoplasia of PCoA and f-PCA, some of the cases also presented with other arterial anomalies. Out of 10 left PCoA hypoplastic cases, 2 cases were associated with hypoplastic right vertebral artery (Fig. 4A, B), right A1 segment of ACA and right f-PCA (Fig. 4B) and left A1 segment of ACA (Fig. 1B). Similarly on right PCoA hypoplasia, 6 out of 16 cases were identified with hypoplastic A1 segment of ACA. In total of 37 bilateral hypoplastic PCoA, 4 were associated with hypoplastic A1 segment of ACA (Fig. 1B) and one cases was found to be associated with vertebral artery hypoplasia (Fig. 4A).

The CW is the main source of blood supply to major parts of the brain, in which various patterns of its formation and number of anatomical variations have been reported till date in the literature. In most variations of the CW, brain function may not be affected due to the collateral circulation and compensation of the blood supply from the contralateral side. In a study of 1,000 brain specimens, 45.2% of typical and 54.8% variations of the CW were reported [8].

The PCoA is an important artery establishing collateral circulation between the anterior and posterior part of CW. This artery also acts as an exit port for thalamoperforating artery, in which the important branch is pre-mamillary or thalamotuberal artery [9] which supplies the floor of 3rd ventricle, thalamus, hypothalamus, mammillary bodies, tuber cinereum, optic tract, pituitary stalk, cerebral peduncle and posterior perforated substance [10]. According to a previous report, aplasia of the right PCoA (16.6%) is more common than the left (3.3%) which is in accordance with the present study [11]. PCoA hypoplasia was found to have a pathophysiological role in stroke with or without carotid artery occlusion [6]. Out of all the branches of CW, a single branch occlusion might not lead to ischemia, because the collateral supply of that particular region will take over the function [12]. However, PCoA hypoplasia would be prone for the ischemia since its perforating branches might be scarcely perfused in cases of PCoA hypoplasia, predisposing thalamic infarctions leading to lacunar stroke [13]. PCoA hypoplasia as an independent or in association with anterior communicating artery and vertebral artery as observed in the present study can be suggested as a risk factor for ischemic stroke [14, 15].

In a study of classical CW, 10% of aplasia, hypoplasia or double PCoA have been reported, stressing the importance of PCoA in vertebral artery hypoplasia which results in stroke [16]. However, in the present study double PCoA has not been observed. But one case of vertebral artery hypoplasia along with bilateral PCoA hypoplasia has been noticed. Vertebral artery hypoplasia or occlusion is rarely symptomatic because there will be a sufficient collateral circulation from the contralateral side through CW. But in conditions of bilateral PCoA and one of the vertebral artery hypoplasia, size and patency of these collateral pathways may be a risk factor for developing cerebral infarction [17].

In the present study, 13 cases of f-PCA were observed with the incidence of 5.6% which is in accordance with the previous literature [18-20].

On the embryological background of CW, the cerebral arteries begin approximately at 5 weeks of gestation. At this stage, many intracranial arteries develop, branch and anastomoses and certain arteries regress among themselves to maintain and to alter towards the adult type of arrangement [21, 22]. The anterior part of CW originates from ICA which divides into cranial and caudal arteries while the posterior part from bilateral longitudinal neural arteries. The caudal part forms the PCoA, the carotid-vertebrobasilar communicating artery. Initially PCA represents a branch of primitive ICA which then arises from basilar artery when vertebrobasilar system develops as the occipital lobes enlarge and its functional demand increases [23-25]. Around 22 weeks PCoA or P1 segment of PCA may enlarges to meet the supply of posterior cerebral circulation and there found to be a continuous alteration of blood flow between carotid and vertebrobasilar system until the growth of brain is fulfilled. According to Padget [26], embryogenesis of CW takes place in two stages, first development of numerous arterial plexuses and regression of certain arterial segments in-utero or postnatal, transforming itself into adult type [27]. The posterior part of CW being more anomalous and variant, the posterior part of brain benefit from more blood supply when compared to the anterior part [28, 29].

In a study of functional PCoA in posterior circulation ischemia, revealed that the blood flow volume in PCoA can compensate for the decreased flow of BA circulation to a certain degree and play a protective role in posterior cerebral ischemia [30]. According to literature, a complete absence of PCA was never been reported, but its origin from BA or ICA only varies [31].

In the present study bilateral hypoplasia of PCoA was found more than unilateral cases which can be taken into consideration as one of the risk factors for the development of stroke. The percentage of stroke was found to be 60% in case of bilateral absence of PCoA, 40% in unilateral absence of PCoA and 20% in patients having both PCoA [16]. In union with A1 segment of ACA and VA hypoplasia either unilateral or bilateral PCoA can result in headaches, hypertension, vertigo, pulsatile tinnitus and posterior circulation stroke [32, 33].

The limitation of the study is that, the difficulty to sort out extremely smaller branches which take part in the collateral circulation to rule out the exact diagnosis such as the CIS. The study also included a limited number of patients which in a larger population can provide even much higher rate of variations and a diverse way of diagnostic approach towards PCoA and its associated anomalies.

Under any major arterial occlusion, the collateral circulation plays a key role and takes over the supply of that deficient vessel thereby reducing the risk of stroke or any occlusive diseases of brain. In such conditions, collateral circulation will be more effective when there is a complete CW with the presence of anterior and PCoA. If any one of these vessels is absent or dysfunction, then collateral circulation will be impaired. In ICA occlusion circulation from the contralateral ICA may be achieved by the presence of patent anterior communicating artery [34]. Collateral flow is enabled via the PCoA from the vertebra basilar system thereby aiding perfusion.

Hypoplastic PCoA should be the highly prioritized and monitored arteries in high risk group’s patients with brain tumours, trauma injuries and cardiovascular complications.

The PCoA, being the main conduit between internal carotid and vertebrobasilar arterial systems, any type of variation of its own and its related structures such as anterior communicating artery PCA or VA as observed in the present study can be a significant record for clinicians and neurosurgeons intended to neurological procedures.

Conceptualization: SPB, SP, DKS. Data acquisition: SP, SPB. Data analysis or interpretation: SPB, SP, DKS. Drafting of the manuscript: SPB, DKS. Critical revision of the manuscript: SPB, SP, DKS. Approval of the final version of the manuscript: all authors.

No potential conflict of interest relevant to this article was reported.

  1. Khazaei M, Salehi H. Protective effect of falcaria vulgaris extract on ethanol induced gastric ulcer in rat. Iran J Pharmacol Ther 2006;5:43-6.
  2. Bayir Y, Odabasoglu F, Cakir A, Aslan A, Suleyman H, Halici M, Kazaz C. The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid. Phytomedicine 2006;13:584-90.
    Pubmed CrossRef
  3. Bonamin F, Moraes TM, Dos Santos RC, Kushima H, Faria FM, Silva MA, Junior IV, Nogueira L, Bauab TM, Souza Brito AR, da Rocha LR, Hiruma-Lima CA. The effect of a minor constituent of essential oil from Citrus aurantium: the role of β-myrcene in preventing peptic ulcer disease. Chem Biol Interact 2014;212:11-9.
    Pubmed CrossRef
  4. Lima ZP, Severi JA, Pellizzon CH, Brito AR, Solis PN, Cáceres A, Girón LM, Vilegas W, Hiruma-Lima CA. Can the aqueous decoction of mango flowers be used as an antiulcer agent? J Ethnopharmacol 2006;106:29-37.
    Pubmed CrossRef
  5. Valle JD. Peptic ulcer disease and related disorders. In: Fauci AS, Harrison TR, editors. Harrison's principles of internal medicine. 17th ed. New York: McGraw-Hill; 2008. p. 1855-1872.
  6. Dimaline R, Varro A. Attack and defence in the gastric epithelium- a delicate balance. Exp Physiol 2007;92:591-601.
    Pubmed CrossRef
  7. Yeomans ND. The ulcer sleuths: the search for the cause of peptic ulcers. J Gastroenterol Hepatol 2011;26 Suppl 1:35-41.
    Pubmed CrossRef
  8. Wallace JL, Miller MJ. Nitric oxide in mucosal defense: a little goes a long way. Gastroenterology 2000;119:512-20.
    Pubmed CrossRef
  9. Ohta Y, Nishida K. Protective effect of coadministered superoxide dismutase and catalase against stress-induced gastric mucosal lesions. Clin Exp Pharmacol Physiol 2003;30:545-50.
    Pubmed CrossRef
  10. Aragón JP, Condit ME, Bhushan S, Predmore BL, Patel SS, Grinsfelder DB, Gundewar S, Jha S, Calvert JW, Barouch LA, Lavu M, Wright HM, Lefer DJ. Beta3-adrenoreceptor stimulation ameliorates myocardial ischemia-reperfusion injury via endothelial nitric oxide synthase and neuronal nitric oxide synthase activation. J Am Coll Cardiol 2011;58:2683-91.
    Pubmed KoreaMed CrossRef
  11. Sorrentino SA, Doerries C, Manes C, Speer T, Dessy C, Lobysheva I, Mohmand W, Akbar R, Bahlmann F, Besler C, Schaefer A, Hilfiker-Kleiner D, Lüscher TF, Balligand JL, Drexler H, Landmesser U. Nebivolol exerts beneficial effects on endothelial function, early endothelial progenitor cells, myocardial neovascularization, and left ventricular dysfunction early after myocardial infarction beyond conventional β1-blockade. J Am Coll Cardiol 2011;57:601-11.
    Pubmed CrossRef
  12. Fonseca VA. Effects of beta-blockers on glucose and lipid metabolism. Curr Med Res Opin 2010;26:615-29.
    Pubmed CrossRef
  13. Corsini A, Maggi FM, Catapano AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res 1995;31:9-27.
  14. Liao JK. Effects of statins on 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition beyond low-density lipoprotein cholesterol. Am J Cardiol 2005;96(5A):24F-33F.
    Pubmed KoreaMed CrossRef
  15. Trochu JN, Mital S, Zhang Xp, Xu X, Ochoa M, Liao JK, Recchia FA, Hintze TH. Preservation of NO production by statins in the treatment of heart failure. Cardiovasc Res 2003;60:250-8.
    Pubmed KoreaMed CrossRef
  16. Schrör K, Löbel P, Steinhagen-Thiessen E. Simvastatin reduces platelet thromboxane formation and restores normal platelet sensitivity against prostacyclin in type IIa hypercholesterolemia. Eicosanoids 1989;2:39-45.
  17. Ungureanu D, Filip C, Artenie A, Artenie R. Evaluation of simvastatin antioxidant effects. Rev Med Chir Soc Med Nat Iasi 2003;107:66-71.
  18. Institute for Laboratory Animal Research, National Academies Press. Guide for the care and use of laboratory animals. 8th ed. Washington: National Academies Press; 2011. p. 220.
  19. Dronjak S, Gavrilović L, Filipović D, Radojcić MB. Immobilization and cold stress affect sympatho-adrenomedullary system and pituitary-adrenocortical axis of rats exposed to long-term isolation and crowding. Physiol Behav 2004;81:409-15.
    Pubmed CrossRef
  20. Das D, Banerjee RK. Effect of stress on the antioxidant enzymes and gastric ulceration. Mol Cell Biochem 1993;125:115-25.
    Pubmed CrossRef
  21. Bahgat AK. Gastroprotective effect of L-carnitine on indomethacin-induced gastric ulcer in rats: the involvement of antioxidant mechanisms and nitric oxide. Med J Cairo Univ 2009;77:43-51.
  22. Abd El Motteleb DM, Hasan MM. Gastroprotective effect of simvastatin against experimentally induced gastric ulcers in rats: role of ATP-sensitive K+ channels. J Am Sci 2011;7:760-8.
  23. Morsy MA, Heeba GH, Abdelwahab SA, Rofaeil RR. Protective effects of nebivolol against cold restraint stress-induced gastric ulcer in rats: role of NO, HO-1, and COX-1,2. Nitric Oxide 2012;27:117-22.
    Pubmed CrossRef
  24. Vane JR. A sensitive method for the assay of 5-hydroxytryptamine. Br J Pharmacol Chemother 1957;12:344-9.
    Pubmed CrossRef
  25. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
    Pubmed CrossRef
  26. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-7.
  27. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130-9.
  28. Hamberg M, Samuelsson B. Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis. Proc Natl Acad Sci U S A 1973;70:899-903.
    Pubmed KoreaMed CrossRef
  29. Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001;5:62-71.
    Pubmed CrossRef
  30. Zhang H, Li X, Ding J, Xu H, Dai X, Hou Z, Zhang K, Sun K, Sun W. Delivery of ursolic acid (UA) in polymeric nanoparticles effectively promotes the apoptosis of gastric cancer cells through enhanced inhibition of cyclooxygenase 2 (COX-2). Int J Pharm 2013;441:261-8.
    Pubmed CrossRef
  31. Altman GD. Three or more independent groups of observations. In: Altman GD, editor. Practical statistics for medical research. 2nd ed. London: Chapman & Hall; 2005. p. 205-17.
  32. Kwiecień S, Brzozowski T, Konturek SJ. Effects of reactive oxygen species action on gastric mucosa in various models of mucosal injury. J Physiol Pharmacol 2002;53:39-50.
    Pubmed CrossRef
  33. Brzozowski T, Konturek PC, Pajdo R, Ptak-Belowska A, Kwiecien S, Pawlik M, Drozdowicz D, Sliwowski Z, Brzozowski B, Konturek SJ, Pawlik WW. Physiological mediators in nonsteroidal anti-inflammatory drugs (NSAIDs)-induced impairment of gastric mucosal defense and adaptation. Focus on nitric oxide and lipoxins. J Physiol Pharmacol 2008;59 Suppl 2:89-102.
  34. Haendeler J, Hoffmann J, Zeiher AM, Dimmeler S. Antioxidant effects of statins via S-nitrosylation and activation of thioredoxin in endothelial cells: a novel vasculoprotective function of statins. Circulation 2004;110:856-61.
    Pubmed CrossRef
  35. Tariq M, Khan HA, Elfaki I, Arshaduddin M, Al Moutaery M, Al Rayes H, Al Swailam R. Gastric antisecretory and antiulcer effects of simvastatin in rats. J Gastroenterol Hepatol 2007;22:2316-23.
    Pubmed CrossRef
  36. Matsui H, Shimokawa O, Kaneko T, Nagano Y, Rai K, Hyodo I. The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. J Clin Biochem Nutr 2011;48:107-11.
    Pubmed KoreaMed CrossRef
  37. Bjarnason I, Scarpignato C, Takeuchi K, Rainsford KD. Determinants of the short-term gastric damage caused by NSAIDs in man. Aliment Pharmacol Ther 2007;26:95-106.
    Pubmed CrossRef
  38. Ma L, Wallace JL. Endothelial nitric oxide synthase modulates gastric ulcer healing in rats. Am J Physiol Gastrointest Liver Physiol 2000;279:G341-6.
    Pubmed KoreaMed CrossRef
  39. Kato S, Ohkawa F, Ito Y, Amagase K, Takeuchi K. Role of endothelial nitric oxide synthase in aggravation of indomethacin-induced gastric damage in adjuvant arthritic rats. J Physiol Pharmacol 2009;60:147-55.
  40. Cho CH. Current roles of nitric oxide in gastrointestinal disorders. J Physiol Paris 2001;95:253-6.
  41. Lanas A. Role of nitric oxide in the gastrointestinal tract. Arthritis Res Ther 2008;10(Suppl 2):S4.
    Pubmed CrossRef
  42. Goel R, Goel A, Manocha A, Pillai KK, Srivastava RS. Influence of nebivolol on anticonvulsant effect of lamotrigine. Indian J Pharmacol 2009;41:41-6.
    Pubmed KoreaMed CrossRef
  43. Ceron CS, Rizzi E, Guimarães DA, Martins-Oliveira A, Gerlach RF, Tanus-Santos JE. Nebivolol attenuates prooxidant and profibrotic mechanisms involving TGF-β and MMPs, and decreases vascular remodeling in renovascular hypertension. Free Radic Biol Med 2013;65:47-56.
    Pubmed CrossRef
  44. Rizzi E, Guimaraes DA, Ceron CS, Prado CM, Pinheiro LC, Martins-Oliveira A, Gerlach RF, Tanus-Santos JE. β1-Adrenergic blockers exert antioxidant effects, reduce matrix metalloproteinase activity, and improve renovascular hypertension-induced cardiac hypertrophy. Free Radic Biol Med 2014;73:308-17.
    Pubmed CrossRef
  45. Dursun S, Çuhadar S, Köseoğlu M, Atay A, Aktaş SG. The anti-inflammatory and antioxidant effects of pravastatin and nebivolol in rat aorta. Anadolu Kardiyol Derg 2014;14:229-33.
    Pubmed CrossRef
  46. Uzar E, Acar A, Evliyaoğlu O, Fırat U, Kamasak K, Göçmez C, Alp H, Tüfek A, Taşdemir N, Ilhan A. The anti-oxidant and anti-apoptotic effects of nebivolol and zofenopril in a model of cerebral ischemia/reperfusion in rats. Prog Neuropsychopharmacol Biol Psychiatry 2012;36:22-8.
    Pubmed CrossRef
  47. Whaley-Connell A, Habibi J, Johnson M, Tilmon R, Rehmer N, Rehmer J, Wiedmeyer C, Ferrario CM, Sowers JR. Nebivolol reduces proteinuria and renal NADPH oxidase-generated reactive oxygen species in the transgenic Ren2 rat. Am J Nephrol 2009;30:354-60.
    Pubmed KoreaMed CrossRef
  48. Abd Allah OM, Sharaf El-Din AAI. Nebivolol ameliorates indomethacin-induced gastric ulcer in adult albino rats: role of inducible nitric oxide synthase. Egypt J Forensic Sci Appli Toxicol 2016;16:147-67.
  49. Parenti A, Filippi S, Amerini S, Granger HJ, Fazzini A, Ledda F. Inositol phosphate metabolism and nitric-oxide synthase activity in endothelial cells are involved in the vasorelaxant activity of nebivolol. J Pharmacol Exp Ther 2000;292:698-703.
  50. Kalinowski L, Dobrucki LW, Szczepanska-Konkel M, Jankowski M, Martyniec L, Angielski S, Malinski T. Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: a novel mechanism for antihypertensive action. Circulation 2003;107:2747-52.
    Pubmed CrossRef
  51. Zhou X, Ma L, Habibi J, Whaley-Connell A, Hayden MR, Tilmon RD, Brown AN, Kim JA, Demarco VG, Sowers JR. Nebivolol improves diastolic dysfunction and myocardial remodeling through reductions in oxidative stress in the Zucker obese rat. Hypertension 2010;55:880-8.
    Pubmed KoreaMed CrossRef
  52. Manrique C, Lastra G, Habibi J, Pulakat L, Schneider R, Durante W, Tilmon R, Rehmer J, Hayden MR, Ferrario CM, Whaley-Connell A, Sowers JR. Nebivolol improves insulin sensitivity in the TGR(Ren2)27 rat. Metabolism 2011;60:1757-66.
    Pubmed KoreaMed CrossRef
  53. Martin GR, Wallace JL. Gastrointestinal inflammation: a central component of mucosal defense and repair. Exp Biol Med (Maywood) 2006;231:130-7.
    Pubmed CrossRef
  54. Vaseem A, Ali M, Afshan K. Activity of Tulsi leaves (Ocimum sanctum linn) in protecting gastric ulcer in rats by cold restrain method. Int J Basic Clin Pharmacol 2017;6:2343-7.
  55. Godara R, Katoch R, Yadav A, Ahanger RR, Bhutyal AD, Verma PK, Katoch M, Dutta S, Nisa F, Singh NK. In vitro acaricidal activity of ethanolic and aqueous floral extracts of Calendula officinalis against synthetic pyrethroid resistant Rhipicephalus (Boophilus) microplus. Exp Appl Acarol 2015;67:147-57.
    Pubmed CrossRef
  56. Banfi C, Baetta R, Gianazza E, Tremoli E. Technological advances and proteomic applications in drug discovery and target deconvolution: identification of the pleiotropic effects of statins. Drug Discov Today 2017;22:848-69.
    Pubmed CrossRef
  57. Heeba GH, Hassan MK, Amin RS. Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: role of nitric oxide and prostaglandins. Eur J Pharmacol 2009;607:188-93.
    Pubmed CrossRef
  58. Liao WC, Huang MZ, Wang ML, Lin CJ, Lu TL, Lo HR, Pan YJ, Sun YC, Kao MC, Lim HJ, Lai CH. Statin decreases Helicobacter pylori burden in macrophages by promoting autophagy. Front Cell Infect Microbiol 2017;6:203.
    Pubmed CrossRef
  59. Lin CJ, Liao WC, Chen YA, Lin HJ, Feng CL, Lin CL, Lin YJ, Kao MC, Huang MZ, Lai CH, Kao CH. Statin therapy is associated with reduced risk of peptic ulcer disease in the Taiwanese population. Front Pharmacol 2017;8:210.
    Pubmed KoreaMed CrossRef
  60. Han ME, Oh SO. Gastric stem cells and gastric cancer stem cells. Anat Cell Biol 2013;46:8-18.
    Pubmed CrossRef
  61. Elwood PC, Gallagher AM, Duthie GG, Mur LA, Morgan G. Aspirin, salicylates, and cancer. Lancet 2009;373:1301-9.
  62. Warzecha Z, Ceranowicz P, Dembinski M, Cieszkowski J, Ginter G, Ptak-Belowska A, Dembinski A. Involvement of cyclooxygenase-1 and cyclooxygenase-2 activity in the therapeutic effect of ghrelin in the course of ethanol-induced gastric ulcers in rats. J Physiol Pharmacol 2014;65:95-106.
  63. El-Ashmawy NE, Khedr EG, El-Bahrawy HA, Selim HM. Nebivolol prevents indomethacin-induced gastric ulcer in rats. J Immunotoxicol 2016;13:580-9.
    Pubmed CrossRef
  64. Rizos E, Bairaktari E, Kostoula A, Hasiotis G, Achimastos A, Ganotakis E, Elisaf M, Mikhailidis DP. The combination of nebivolol plus pravastatin is associated with a more beneficial metabolic profile compared to that of atenolol plus pravastatin in hypertensive patients with dyslipidemia: a pilot study. J Cardiovasc Pharmacol Ther 2003;8:127-34.
    Pubmed CrossRef

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