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(Hypertension. 1999;34:1254.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Interaction Between Nitric Oxide and Endogenous Vasoconstrictors in Control of Renal Blood Flow

Heike Berthold; Armin Just; Hartmut R. Kirchheim; Heimo Ehmke

From I. Physiologisches Institut der Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.

Correspondence to Dr Heimo Ehmke, I. Physiologisches Institut der Ruprecht-Karls Universität, Im Neuenheimer Feld 326, D-69120 Heidelberg, Germany. E-mail ehmke{at}novsrv1.pio1.uni-heidelberg.de

Abstract—The level of renal blood flow (RBF) is controlled by opposing vasoconstrictor and vasodilator influences. In a recent investigation in normotensive dogs, we found that combined blockade of endothelin type A (ET_A) receptors and angiotensin II formation induces marked increases in RBF that were much larger than the effects of blocking either system alone. The aim of the present study was to determine the contribution of nitric oxide (NO) to this vasodilator response. Experiments were made in 6 conscious, chronically instrumented dogs subjected to 5 different experimental treatments on separate days. Blockade of ET_A receptors alone by the selective antagonist LU 135252 had only minor effects on RBF compared with time-control experiments. Additional blockade of angiotensin II formation by angiotensin-converting enzyme inhibition with trandolaprilat caused a substantial increase of RBF by 50%. This vasodilation was entirely suppressed when NO formation was prevented by inhibition of NO synthase with N^G-nitro-L-arginine methyl ester HCl. However, when during NO synthase inhibition renal vascular NO concentrations were clamped at control levels by infusing the NO donor S-nitroso-N-acetyl-D,L-penicillamine, the vasodilator response to combined blockade of ET_A receptors and angiotensin II formation was completely restored (RBF 60%). These results indicate that the vasodilation after combined ET_A receptor blockade and angiotensin-converting enzyme inhibition is not mediated by an increase in NO release but results from the unmasking of the tonic influence that is normally exerted by constitutively released NO. Accordingly, the tonic activity of endothelial NO synthase appears to be of major importance in the physiological regulation of renal vascular resistance by determining the vasomotor responses to endothelin and angiotensin II.

Key Words: endothelin • receptors, endothelin • nitric oxide • renal circulation • renin-angiotensin system

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