C-type natriuretic peptide. An endogenous inhibitor of vascular angiotensin-converting enzyme activity

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.

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 microgram/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.

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