Losartan but Not Verapamil Inhibits Angiotensin II–Induced Tissue Endothelin-1 Increase

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Abstract
Abstract —Endothelin partially mediates angiotensin (Ang) II–induced vascular changes in vivo. This study investigated the effects of the angiotensin type 1 receptor antagonist losartan and the calcium channel blocker verapamil on vascular reactivity and tissue endothelin-1 levels in aortas of Wistar-Kyoto rats treated for 2 weeks with Ang II (200 ng · kg −1 · min −1 ). Ang II increased systolic blood pressure (39±4 mm Hg, P P P P P r =−0.733, P P <0.05). Ang II–induced hypertension enhanced endothelium-dependent contractions to acetylcholine, and these were normalized by either drug. In conclusion, these findings suggest that long-term treatment with Ang II modulates endothelin-1 protein expression in the rat aorta. Although both antihypertensive agents lowered blood pressure and normalized endothelial function, only losartan prevented the increase in tissue endothelin-1 content, suggesting that angiotensin type 1 receptor antagonists but not calcium antagonists modulate tissue endothelin-1 in vivo.