Chronic therapy with the selective endothelin A receptor antagonist LU135252 partially prevented angiotensin II-induced hypertension and alterations of endothelial function in rats (P < .05).
Does LU135252 reduce blood pressure and improve endothelial function in rats with angiotensin II-induced hypertension?
Chronic ET_A-receptor blockade with LU135252 partially prevents angiotensin II-induced hypertension and endothelial dysfunction in a rat model.
p-value: p=<.05
Angiotensin II, a constrictor and mitogen of vascular smooth muscle cells, affects the release of endothelium-derived factors such as nitric oxide or endothelin-1. This study investigated the influence of endothelin-1, using the selective endothelin A receptor antagonist LU135252, on blood pressure and endothelial function in angiotensin II-induced hypertension in the rat. Two weeks of angiotensin II administration (200 ng/kg per minute) increased systolic blood pressure (+35 +/- 5 mm Hg; tail-cuff method) compared with placebo (P < .05). LU135252 alone did not affect systolic pressure but lowered the angiotensin II-induced pressure increase (P < .05). In isolated aortic rings, endothelium-dependent relaxations to acetylcholine were reduced in the angiotensin II group (P < .05 versus placebo) and improved by concomitant chronic LU135252 treatment (P < .05 versus angiotensin II). Blood pressure elevation strongly correlated with impaired endothelium-dependent relaxations to acetylcholine (r = -.967). LU135252 did not affect endothelium-independent relaxations to sodium nitroprusside, which were diminished after angiotensin II treatment (P < .05). In quiescent rings, chronic angiotensin II administration enhanced endothelium-dependent contractions to acetylcholine, which were reduced by LU135252 (P < .05). Impaired contractions to endothelin-1 and norepinephrine in the angiotensin II group were normalized after treatment with LU135252 (P < .05). Thus, chronic therapy with LU135252 partially prevents angiotensin II-induced hypertension and the alternations of the endothelial function observed in this experimental model.
d’Uscio et al. (Wed,) conducted a other in Angiotensin II-induced hypertension. LU135252 vs. Placebo / Angiotensin II alone was evaluated on Systolic blood pressure and endothelial function (p=<.05). Chronic therapy with the selective endothelin A receptor antagonist LU135252 partially prevented angiotensin II-induced hypertension and alterations of endothelial function in rats (P < .05).