The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta

Erol, Kevser; Özatik, Fikriye Yasemin; KAYGISIZ, Bilgin

The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta

FİKRİYE YASEMİN ÖZATİK, (Department of Pharmacology, Ahi Evran University School of Medicine, Kırşehir, Turkey)

Bilgin KAYGISIZ, (Department of Pharmacology, Eskişehir Osmangazi University School of Medicine, Eskişehir, Turkey)

Kevser EROL (Department of Pharmacology, Eskişehir Osmangazi University School of Medicine, Eskişehir, Turkey)

Eurasian Journal of Medicine

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Yıl: 2017 Cilt: 49 Sayı: 1 Sayfa Aralığı: 16 - 21 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta

Öz:

Amaç: Siklooksijenaz (COX) enzimleri tarafından sentezlenen prostaglandinlerin anjiotensin dönüştürücü enzim (ADE) inhibisyonu ve anjiotensin AT1 reseptör antagonizmasının etkilerine katkıda bulunduğu ve ADE sinyal yolakları ile COX enzimleri arasında etkileşme olduğu ileri sürülmüştür. Bu çalışmada anjiotensin II (Ang II) reseptör antagonisti bir ilaç olan losartan veya ADE inhibitörü bir ilaç olan lizinoprilin izole organ banyosunda sıçan torasik aorta kasılmaları üzerindeki etkilerinde COX enzimlerinin rolünün araştırılmasını amaçladık. Gereç ve Yöntem: Losartan (10-6,10-5,10-4M), lizinopril (10-6,10-5,10-4M) ve selektif olmayan bir COX inhibitörü olan dipironun (10-4,7x10-4,2x10-3M) tek başına fenilefrin (Phe) (10-7M), potasyum klorür (KCl) (6x10-2M) ve Ang II (10-8M) ile indüklenen kasılmalar üzerindeki ve ayrıca losartan veya lizinoprilin dipironla kombinasyonlarının Phe veya KCl ile indüklenen kasılmalar üzerindeki yanıtları kaydedildi. Bulgular: Tek başlarına verildiklerinde dipiron ve losartan Phe, KCl ve Ang II ile indüklenen kasılmaları baskılarken, lizinopril sadece Phe ve Ang II ile indüklenen kasılmaları baskıladı. COX enzimlerinin inhibisyonu (dipiron 10-4,7x10-4,2x10-3M tarafından sırasıyla COX-3, COX-3+-1, COX1+-2+3), losartan veya lizinoprilin gevşetici etkilerini artırdı. Ayrıca dipiron, lizinoprilin KCl ile indüklenen kasılmalar üzerindeki etkisini potansiyalize etti. Sonuç: Dipironun losartan veya lizinoprilin düz kas gevşetici etkilerini artırdığını ve COX enzim inhibisyonunun bu gevşemede rolü olabileceğini ileri sürüyoruz

Anahtar Kelime:

Konular: Genel ve Dahili Tıp

Losartan ve Lizinoprilin Sıçan Torasik Aort Kasılmaları Üzerindeki Etkilerinde Siklooksijenaz Enzimlerinin Rolü

Öz:

Objective: It was suggested that prostaglandins which are synthesized by cyclooxygenase (COX) enzymes contribute to the actions of angiotensin-converting enzyme (ACE) inhibition and angiotensin AT1 receptor antagonism and there is an interaction between ACE signaling pathway and COX enzymes. We aim to investigate the role of COX enzymes in the effects of losartan, an angiotensin II (Ang II) receptor antagonist or lisinopril, an ACE inhibitor, on the contractions of rat thoracic aorta in isolated tissue bath. Materials and Methods: Responses of losartan (10-6, 10-5, 10-4 M), lisinopril (10-6, 10-5, 10-4 M), and non-selective COX inhibitor dipyrone (10-4, 7 × 10-4, 2 × 10-3 M) alone to the contractions induced by phenylephrine (Phe) (10-7 M), potassium chloride (KCl) (6 × 10-2 M), Ang II (10-8 M) and responses of losartan or lisinopril in combination with dipyrone to the contractions induced by Phe or KCl were recorded. Results: When used alone, dipyrone and losartan inhibited Phe, KCl, and Ang II-induced contractions, whereas lisinopril inhibited only Phe and Ang II-induced contractions. Inhibition of COX enzymes (COX-3, COX-3 + COX-1, COX-1+ COX-2 + COX-3 by dipyrone 10-4, 7 × 10-4, 2 × 10-3 M, respectively) augmented the relaxant effects of losartan or lisinopril. Also, dipyrone potentiated the effect of lisinopril on KCl-induced contractions. Conclusion: We suggest that dipyrone increases the smooth-muscle relaxing effects of losartan or lisinopril and that COX enzyme inhibition may have a role in the enhancement of this relaxation

Anahtar Kelime:

Konular: Genel ve Dahili Tıp

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Galán M, Miguel M, Beltrán AE, et al. Angiotensin II differentially modulates cyclooxygenase-2, microsomal prostaglandin E2 synthase 1 and prostaglandin I2 synthase expression in advential fibroblasts exposed toinflammatory stimuli. J Hypertens 2011; 29: 529-36. [CrossRef]
2. Kamo T, Akazawa H, Komuro I. Pleiotropic effects of angiotensin ıı receptor signaling in cardiovascular homeostasis and aging. Int Heart J 2015; 56: 249-54. [CrossRef]
3. Sica DA, Gehr TW, Ghosh S. Clinical pharmacokinetics of losartan. Clin Pharmacokinet 2005; 44: 797-814. [CrossRef]
4. Iyer SN, Yamada K, Diz DI, Ferrario CM, Chappell MC. Evidence that prostaglandins mediate the antihypertensive actions of angiotensin-(1-7) during chronic blockade of the renin-angiotensin system. J Cardiovasc Pharmacol 2000; 36: 109-17. [CrossRef]
5. D’Abril Ruíz-Leyja E, Villalobos-Molina R, LópezGuerrero JJ, Gallardo-Ortíz IA, Estrada-Soto SE, Ibarra-Barajas M. Differential role of cyclooxygenase-1 and -2 on renal vasoconstriction to α1-adrenoceptor stimulation in normotensive and hypertensive rats. Life Sci 2013; 93: 552-7. [CrossRef]
6. Rubio-Ruiz ME, Pérez-Torres I, Diaz-Diaz E, Pavón N, Guarner-Lans V. Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats. Acta Pharmacol Sin 2014; 35: 1364-74. [CrossRef]
7. Chandrasekharan NV, Dai H, Roos KL, et al. COX- 3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci USA 2002; 99: 13926-31. [CrossRef]
8. Albayrak A, Alp HH, Suleyman H. Investigation of antiulcer and antioxidant activity of moclobemide in rats. Eurasian J Med 2015; 47: 32-40. [CrossRef]
9. Kis B, Snipes JA, Busija DW. Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties. J Pharmacol Exp Ther 2005; 315: 1-7. [CrossRef]
10. Snipes JA, Kis B, Shelness GS, Hewett JA, Busija DW. Cloning and characterization of cyclooxygenase-1b (putative COX-3) in rat. J Pharmacol Exp Ther 2005; 313: 668-76. [CrossRef]
11. Patrono C. Cardiovascular effects of cyclooxygenase-2 ınhibitors: a mechanistic and clinical perspective. Br J Clin Pharmacol 2016; 82: 957-64. [CrossRef]
12. Conaghan PG. A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity. Rheumatol Int 2012; 32: 1491-502. [CrossRef]
13. Castillo-Hernández MC, Martinez-Godinez MA, Guevara-Balcazar G, et al. Extraendothelial and constitutive COX-2 expression is involved in the contractile effect of angiotensin II in the rat aorta. Auton Autacoid Pharmacol 2010; 30: 205-11. [CrossRef]
14. Park BM, Gao S, Cha SA, Kim SH. Attenuation of renovascular hypertension by cyclooxygenase-2 inhibitor partly through ANP release. Peptides 2015; 69: 1-8. [CrossRef]
15. Zhou QL, Peng WS, Yuichiro Y, Liu ZC, Yang JH. Effect of losartan on cyclooxygenase-2 expression in normal human mesangial cells and kidneys of rats with diabetic nephropathy. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2008; 33: 790-9.
16. Kohlstedt K, Busse R, Fleming I. Signaling via the angiotensin-converting enzyme enhances the expression of cyclooxygenase-2 in endothelial cells. Hypertension 2005; 45: 126-32. [CrossRef]
17. Bawolak MT, Touzin K, Moreau ME, Désormeaux A, Adam A, Marceau F. Cardiovascular expression of inflammatory signaling molecules, the kinin B1 receptor and COX2, in the rabbit: effects of LPS, anti-inflammatory and anti-hypertensive drugs. Regul Pept 2008; 146: 157-68. [CrossRef]
18. Gryglewski RJ, Chlopicki S, Swies J. In vivo endothelial interaction between ACE and COX inhibitors. Prostaglandins Leukot Essent Fatty Acids 2005; 72: 129-31. [CrossRef]
19. Gülmez SE, Serel S, Uluç A, Can Z, Ergün H. Dipyrone increases the blood flow of arterial dorsal skin flaps. Aesthetic Plast Surg 2008; 32: 766-70. [CrossRef]
20. Erol K, Sirmagul B, Kilic FS, Yigitaslan S, Dogan AE. The role of inflammation and COX-derived prostanoids in the effects of bradykinin on isolated rat aorta and urinary bladder. Inflammation 2012; 35: 420-8. [CrossRef]
21. Marjoribanks J, Ayeleke RO, Farquhar C, Proctor M. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev 2015; (7): CD001751. [CrossRef]
22. Bapna M, Chauhan LS. The ambidextrous cyclooxygenase: an enduring target. Inflamm Allergy Drug Targets 2015; 13: 387-92. [CrossRef]
23. Polzin A, Hohlfeld T, Kelm M, Zeus T. Impairment of aspirin antiplatelet effects by non-opioid analgesic medication. World J Cardiol 2015; 7: 383-91. [CrossRef]
24. Valenzuela F, García-Saisó S, Lemini C, RamírezSolares R, Vidrio H, Mendoza-Fernández V. Metamizol acts as an ATP sensitive potassium channel opener to inhibit the contracting response induced by angiotensin II but not to norepinephrine in rat thoracic aorta smooth muscle. Vascul Pharmacol 2005; 43: 120-7. [CrossRef]
25. Ergün H, Ayhan IH, Tulunay FC. Pharmacological characterization of metamizol-induced relaxation in phenylephrine-precontracted rabbit thoracic aorta smooth muscle. Gen Pharmacol 1999; 33: 237-41. [CrossRef]
26. Loh WM, Ling WC, Murugan DD, et al. Desaspartate angiotensin I (DAA-I) reduces endothelial dysfunction in the aorta of the spontaneously hypertensive rat through inhibition of angiotensin II-induced oxidative stress. Vascul Pharmacol 2015; 71: 151-8. [CrossRef]
27. Santuzzi CH, Tiradentes RV, Mengal V, et al. Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension. Braz J Med Biol Res 2015; 48: 65-76. [CrossRef]
28. Accorsi-Mendonça D, Corrêa FM, Oliveira AM. B(2)-receptor modulation of the reactivity to phenylephrine and angiotensin II in the carotid artery of normotensive rats after trandolapril treatment. J Smooth Muscle Res 2006; 42: 21-31. [CrossRef]
29. Adeagbo AS, Zhang X, Patel D, et al. Cyclooxygenase-2, endothelium and aortic reactivity during deoxycorticosterone acetate salt-induced hypertension. J Hypertens 2005; 23: 1025-36. [CrossRef]
30. Alvarez Y, Pérez-Girón JV, Hernanz R, et al. Losartan reduces the increased participation of cyclooxygenase-2-derived products in vascular responses of hypertensive rats. J Pharmacol Exp Ther 2007; 321: 381-8. [CrossRef]
31. Gonçalves AR, Fujihara CK, Mattar AL, et al. Renal expression of COX-2, ANG II, and AT1 receptor in remnant kidney: strong renoprotection by therapy with losartan and a nonsteroidal anti-inflammatory. Am J Physiol Renal Physiol 2004; 286: F945-54. [CrossRef]
32. Boshra V, El Wakeel GA, Nader MA. Effect of celecoxib on the antihypertensive effect of losartan in a rat model of renovascular hypertension. Can J Physiol Pharmacol 2011; 89: 103-7. [CrossRef]
33. Haefeli WE, Linder L, Lüscher TF. Quinaprilat induces arterial vasodilation mediated by nitric oxide in humans. Hypertension 1997; 30: 912-7. [CrossRef]
34. Yamada Y, Iwasaki M, Usui H, et al. Rapakinin, an anti-hypertensive peptide derived from rapeseed protein, dilates mesenteric artery of spontaneously hypertensive rats via the prostaglandin IP receptor followed by CCK(1) receptor. Peptides 2010; 31: 909-14. [CrossRef]
35. Guzmán-Hernández EA, Villalobos-Molina R, Sánchez-Mendoza MA, Del Valle-Mondragón L, Pastelín-Hernández G, Ibarra-Barajas M. Early coexpression of cyclooxygenase-2 and renin in the rat kidney cortex contributes to the development of N(G)-nitro-L-arginine methyl ester induced hypertension. Can J Physiol Pharmacol 2015; 93: 299-308. [CrossRef]

APA	Özatik F, KAYGISIZ B, Erol K (2017). The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta. , 16 - 21.
Chicago	Özatik Fikriye Yasemin,KAYGISIZ Bilgin,Erol Kevser The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta. (2017): 16 - 21.
MLA	Özatik Fikriye Yasemin,KAYGISIZ Bilgin,Erol Kevser The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta. , 2017, ss.16 - 21.
AMA	Özatik F,KAYGISIZ B,Erol K The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta. . 2017; 16 - 21.
Vancouver	Özatik F,KAYGISIZ B,Erol K The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta. . 2017; 16 - 21.
IEEE	Özatik F,KAYGISIZ B,Erol K "The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta." , ss.16 - 21, 2017.
ISNAD	Özatik, Fikriye Yasemin vd. "The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta". (2017), 16-21.

APA	Özatik F, KAYGISIZ B, Erol K (2017). The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta. Eurasian Journal of Medicine, 49(1), 16 - 21.
Chicago	Özatik Fikriye Yasemin,KAYGISIZ Bilgin,Erol Kevser The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta. Eurasian Journal of Medicine 49, no.1 (2017): 16 - 21.
MLA	Özatik Fikriye Yasemin,KAYGISIZ Bilgin,Erol Kevser The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta. Eurasian Journal of Medicine, vol.49, no.1, 2017, ss.16 - 21.
AMA	Özatik F,KAYGISIZ B,Erol K The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta. Eurasian Journal of Medicine. 2017; 49(1): 16 - 21.
Vancouver	Özatik F,KAYGISIZ B,Erol K The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta. Eurasian Journal of Medicine. 2017; 49(1): 16 - 21.
IEEE	Özatik F,KAYGISIZ B,Erol K "The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta." Eurasian Journal of Medicine, 49, ss.16 - 21, 2017.
ISNAD	Özatik, Fikriye Yasemin vd. "The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta". Eurasian Journal of Medicine 49/1 (2017), 16-21.