Journal
AMERICAN JOURNAL OF HYPERTENSION
Volume 19, Issue 11, Pages 1167-1173Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.amjhyper.2006.04.005
Keywords
salt; endothelium; in vivo; potassium channel; clofibrate
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Background: Endothelium-dependent vascular relaxation is impaired in various disease states including hypertension. Methods: We investigated whether a single bolus dose of clofibrate could rapidly reverse saline-induced endothelial dysfunction, in vivo, in salt-loaded Sprague-Dawley (S-D) rats. S-D rats, 5 weeks of age, were divided into two groups. One group served as a control (Con) and was given tap water; the other group (Sal) was given normal saline (0.9% NaCl) ad libitum for 3 weeks. Results: Mean arterial pressure (MAP) was significantly higher (138 +/- 2 v 112 +/- 2 mm Hg, P <.001), whereas the total plasma nitrite/nitrate levels were lower (1.7 +/- 0.3 v 2.8 +/- 0.2 mu mol/L, P <.05) in Sal. At this time, endothelial function was assessed in vivo. Sal rats had decreased hypotensive responses to acetylcholine (ACh) but maintained normal responses to sodium nitroprusside. The ACh-induced hypotensive response was significantly inhibited by the nitric oxide synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME, 100 mg kg(-1) intraperitoneally [ip]) only in Con rats. Clofibrate (Clof, 200 mg kg(-1) ip) did not change blood pressure but increased ACh-induced hypotensive responses only in Sal, an effect that was abolished by subsequent administration of aparnin (Apa, 50 mu g kg(-1) iv) and charybdotoxin (ChTx, 50 mu g kg(-1) iv). Apa+ChTx blocked responses to ACh in Con and Sal, as expected. A single dose of clofibrate (200 mg kg(-1) ip), given subsequently to Apa+ChTx, restored responses to ACh in both the Con and Sal groups, again without affecting baseline MAP. Conclusion: Clotibrate has an acute salutary effect on endothelium-dependent vasodilation in saline-treated rats, probably mediated through vascular calcium-activated potassium channels and independent of an antihypertensive effect.
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