Clofibrate acutely reverses saline-induced endothelial dysfunction: role of calcium-activated potassium channels.

Abstract:

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 nu 112 +/- 2 mm Hg, P < .001), whereas the total plasma nitrite/nitrate levels were lower (1.7 +/- 0.3 v 2.8 +/- 0.2 micromol/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 apamin (Apa, 50 microg kg(-1) iv) and charybdotoxin (ChTx, 50 microg 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:Clofibrate 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.

journal_name

Am J Hypertens

authors

Sankaralingam S,Desai KM,Wilson TW

doi

10.1016/j.amjhyper.2006.04.005

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

1167-73

issue

11

eissn

0895-7061

issn

1941-7225

pii

S0895-7061(06)00263-9

journal_volume

19

pub_type

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