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(Circulation. 1996;93:1155-1159.)
© 1996 American Heart Association, Inc.

Articles

C-Type Natriuretic Peptide

An Endogenous Inhibitor of Vascular Angiotensin-Converting Enzyme Activity

Neil C. Davidson, MB, MRCP; Craig S. Barr, MB, MRCP; Allan D. Struthers, MD, FRCP

From the Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, UK.

Correspondence to Prof A.D. Struthers, Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, DD1 9SY UK.

Background Atrial and B-type natriuretic peptide are both known to be antagonists of the renin-angiotensin system. C-type natriuretic peptide (CNP) is a new member of this family except that its principal source is the vascular endothelium. This study tested the hypothesis that CNP is a local inhibitor of vascular angiotensin-converting enzyme (ACE) activity.

Methods and Results Vascular ACE activity was assessed by the differential vascular response to angiotensin I and angiotensin II. Healthy male volunteers were studied with the use of brachial artery infusions of angiotensin I and angiotensin II at two doses, with and without coinfusion of CNP at 500 pmol/min (n=8) and hydralazine at 10 µg/min (n=8) (as a nonspecific vasodilator control). CNP alone and hydralazine alone caused similar increases in forearm blood flow (CNP+, 93.0±14.8%; hydralazine+, 84.2±22.6%). CNP inhibited the vasoconstrictive effect of angiotensin I (reduction in overall effect with CNP, 56.8±12.9%; P<.001) but not that of angiotensin II. Hydralazine did not significantly inhibit the effect of either angiotensin I or angiotensin II.

Conclusions This evidence of a differential effect of CNP on the vascular response to angiotensin I but not to angiotensin II suggests that CNP acts as a local endogenous regulator of vascular ACE activity in the human forearm resistance vessels.

Key Words: peptides • angiotensin • natriuretic peptides • atrial natriuretic factor • vasoconstriction

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