(Hypertension. 2000;35:1237.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Interactions Between Nitric Oxide and Endothelin in the Regulation of Vascular Tone of Human Resistance Vessels In Vivo
From the Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Correspondence to Dr Julio A. Panza, Cardiology Branch, National Institutes of Health, Building 10, Room 7B-15, Bethesda, MD 20892. E-mail panzaj{at}nih.gov
Abstract—Endothelial release of nitric oxide (NO) contributes to the regulation of vascular tone by inducing vascular relaxation. In addition, NO may inhibit the synthesis and hemodynamic effects of endothelin-1 (ET-1), a powerful endothelium-derived vasoconstrictor peptide that may stimulate NO production. However, whether NO and ET-1 physiologically interact to regulate vascular tone in humans has not been defined. In this study, the interactions between the L-arginine NO pathway and the ET-1 system in the regulation of vascular tone in human forearm resistance vessels were examined in vivo. Vasomotor response to the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 4 µmol/min for 30 minutes) was measured during either saline infusion or blockade of ET-1 receptors. Endothelin-A (ETA) and endothelin-B (ETB) receptor blockade was achieved by infusion of BQ-123 (100 nmol/min) and BQ-788 (50 nmol/min), respectively, separately and in combination. Drugs were infused into the brachial artery, and the forearm blood flow (FBF) response was measured by strain-gauge plethysmography. During saline infusion, L-NMMA administration significantly decreased FBF (25%, P<0.01 versus baseline). This effect was significantly blunted during nonselective blockade of ET-1 receptors (7% decrease in FBF, P=0.02 versus the effect of L-NMMA during saline infusion). Selective ETA blockade did not modify the vasoconstrictor response to L-NMMA (26% decrease in FBF, P=0.66 versus the effect of L-NMMA during saline infusion), but selective ETB receptor antagonism caused significant diminution of the hemodynamic response to NO inhibition (8% decrease in FBF, P=0.04 versus the effect of L-NMMA during saline infusion). Thus ET-1 contributes to the regulation of vascular tone by stimulating NO activity. This effect is mediated through endothelial ETB receptors and may be relevant in conditions associated with endothelial dysfunction.
Key Words: endothelin • nitric oxide • vascular tone • receptors, endothelin • blood flow
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