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

Abstract

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 x 10(-4), 2 x 10(-3) M) alone to the contractions induced by phenylephrine (Phe) (10(-7) M), potassium chloride (KCl) (6 x 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 x 10(-4), 2 x 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.