Acetylcholine‐induced endothelium‐dependent contractions in the SHR aorta: the Janus face of prostacyclin

Abstract

1 In the spontaneously hypertensive rat (SHR) and aging Wistar-Kyoto rats (WKY), acetylcholine releases an endothelium-derived contracting factor (EDCF) produced by endothelial cyclooxygenase-1, which stimulates thromboxane A 2 receptors (TP receptors) on vascular smooth muscle. The purpose of the present study was to identify this EDCF by measuring changes in isometric tension and the release of various prostaglandins by acetylcholine. 2 In isolated aortic rings of SHR, U 46619, prostaglandin (PG) H 2 , PGF 2a , PGE 2 , PGD 2 , prostacyclin (PGI 2 ) and 8-isoprostane, all activate TP receptors of the vascular smooth muscle to produce a contraction (U 46619)8-isoprostane ¼ PGF 2a ¼ PGH 2 4PGE 2 ¼ PGD 2 4PGI 2 ). The contractions produced by PGH 2 and PGI 2 were fast and transient, mimicking endothelium-dependent contractions. PGI 2 did not relax isolated aortic rings of WKY and SHR. 3 Acetylcholine evoked the endothelium-dependent release of thromboxane A 2 , PGF 2a , PGE 2 , PGI 2 and most likely PGH 2 (PGI 2 )PGF 2a XPGE 2 4TXA 2 48-isoprostane, PGD 2 ). Dazoxiben abolished the production of thromboxane A 2 , but did not influence the endothelium-dependent contractions to acetylcholine. 4 The release of PGI 2 was significantly larger in the aorta of SHR than in WKY, and the former was more sensitive to the contractile effect of PGI 2 than the latter. The inhibition of PGI-synthase was associated with an increase in PGH 2 spillover and the enhancement of acetylcholine-induced endothelium-dependent contractions. 5 Thus, in the aorta of SHR and aging WKY, the endothelium-dependent contractions elicited by acetylcholine most likely involve the release of PGI 2 with a concomitant contribution of PGH 2 .

Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

“…Endothelium-and cyclooxygenase-dependent contractions are prominent in the aorta of the spontaneously hypertensive rat (Lüscher and Vanhoutte, 1986;Yang et al, 2004a, b;Tang et al, 2007), the abdominal aorta of the diabetic rabbit and the femoral artery of the diabetic rat (Shi et al, 2007). The endothelium-derived contracting factor can be prostacyclin, thromboxane A 2 , endoperoxides, prostaglandin E 2 , hydroxyl radicals or superoxide anions depending on the animal model, the preparation and the agonist used Auch-Schwelk et al, 1990;Yang et al, 2004a, b;Gluais et al, 2005Gluais et al, , 2006Shi et al, 2007). Oxygen-derived free radicals facilitate endothelium-dependent contractions, and antioxidants effectively decreased them in the aorta of spontaneously hypertensive rats Yang et al, 2002Yang et al, , 2003bTang et al, 2007).…”

Gene expression changes of prostanoid synthases in endothelial cells and prostanoid receptors in vascular smooth muscle cells caused by aging and hypertension

“…EDCF is unlikely to be a single substance but rather is constituted of a mixture of prostanoids, the formation of which depends on the vascular bed, the age, and the condition of the species studied. Thus prostacyclin (9,10,27), endoperoxides (7,14), and thromboxane A 2 (10,11,29) have been proposed as EDCFs. Cyclooxygenase breaks down arachidonic acid to form endoperoxides, which are subsequently converted into prostacyclin, thromboxane A 2 , prostaglandin D, prostaglandin E, and/or prostaglandin F by their respective synthases (3,20).…”

Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR

“…[3][4][5] In spontaneously hypertensive rats (SHR) a well-described manifestation of endothelial dysfunction is an increased production of endotheliumderived contractile factors (EDCF). 6 Drug-intervention studies have shown that some anti-hypertensive treatments, for instance with angiotensin AT 1 receptor antagonists, not only lower blood pressure but also cause an improvement of endothelial function and regression of structural changes in resistance arteries. 7,8 Other anti-hypertensive treatments, for example, the selective β 1 -adrenoceptor antagonist atenolol, succeed in lowering blood pressure but did not reverse the structural changes or the endothelial dysfunction associated with hypertension.…”