Endothelial vasoconstrictor prostanoids modulate contractions to acetylcholine and ANG II in Ren-2 rats

Abstract

We investigated vascular function in mouse Ren-2 transgenic rats with hypertension. Mesenteric resistance arteries of transgenic and Sprague-Dawley rats (controls) were isolated at ages 6 and 12 wk and suspended in myographs for isometric tension recording. Systolic blood pressure was higher in transgenic than control rats (P < 0.05). Contractions to norepinephrine and endothelin-1 were comparable in transgenic and control rats, but the sensitivity decreased with age in both strains (P < 0.05). Contractions to angiotensin I were comparable in 6-wk-old transgenic rats and controls, but the response to angiotensin I was more pronounced in transgenic rats at 12 wk of age. Contractions to angiotensin II were higher in transgenic rats and decreased with age in both strains. Preincubation with the cyclooxygenase inhibitor meclofenamate or the thromboxane receptor antagonist SQ-30741 blunted the response only in 6-wk-old transgenic rats. In quiescent vascular rings, acetylcholine evoked endothelium-dependent contractions after inhibition of nitric oxide formation by N omega-nitro-L-arginine methyl ester only in transgenic rats. These contractions were inhibited by SQ-30741 (P < 0.05) but not by the thromboxane synthase inhibitor CGS-13080. Contractions to the thromboxane analogue U-46619 were comparable in both strains at the age of 6 wk; sensitivity was increased in transgenic rats at 12 wk (P < 0.05). In conclusion, in mesenteric resistance arteries of Ren-2 transgenic rats I) contractions to angiotensin I and II but not to norepinephrine and endothelin-1 are increased, and 2) acetylcholine as well as angiotensin II modulate endothelium-dependent contractions mediated by prostaglandin H2. These alterations together with increased sensitivity to thromboxane could contribute to maintenance as well as to impaired tissue perfusion of this form of hypertension.