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on July 3, 2003

Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print July 3, 2003, doi: 10.1161/01.ATV.0000084826.86349.1D
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Submitted on May 5, 2003
Accepted on June 2, 2003

Atrial Natriuretic Peptide Regulates Regional Vascular Volume and Venous Tone in Humans

Matthias Schmitt *; Andrew J.M. Broadley ; Angus K. Nightingale ; Nicola Payne ; Prasad Gunaruwan ; Justin Taylor ; Leong Lee ; John Cockcroft ; Allan D. Struthers ; and Michael P. Frenneaux

From the Wales Heart Research Institute, Cardiff, UK; Medical Data Research Centre (N.P.), Providence Health System, Portland, Ore; and Department of Clinical Pharmacology (A.D.S.), Ninewells Hospital, Dundee, UK.

* To whom correspondence should be addressed. E-mail: matthschmitt{at}doctors.org.uk.

Objective--To date, the contribution of basal atrial natriuretic peptide (ANP) levels to resting vascular function in humans is unknown. In the present study we sought to investigate the role of ANP in regulating regional vascular volume and venous tone in healthy subjects.

Methods and Results--We used radionuclide plethysmography to examine the effects of ANP and the ANP-receptor antagonist A71915 on forearm vascular volume. Creating pressure/volume relations, we determined changes in vascular volume, compliance, and tone. Performing dose-ranging studies, we additionally assessed the potency and specificity of A71915 in the forearm resistance vasculature. Equilibrium blood pool scintigraphy was then used to assess the effects of systemic administration of A71915 on regional intestinal vascular volume. Infusion of ANP increased forearm vascular volume in a dose-dependent manner (maximum 20%; P<0.001), exerting a maximum venodilating effect at plasma levels similar to that seen in heart failure. A71915 increased venous tone, thereby decreasing vascular volume by 9.6±1.1%, P<0.001 (forearm), and 2.6±0.5%, P=0.01 (intestinal beds). At an infusion ratio of 50:1, A71915 almost completely abolished the effects of ANP on forearm blood flow.

Conclusions--ANP locally regulates regional vascular volume and tone without affecting compliance.
Key words: veins • vascular volume • A71915 • receptor antagonism




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