Bioactivity and metabolism of C-type natriuretic peptide in normal man.
C-Type natriuretic peptide (CNP) is a recently identified member of the natriuretic peptide family with potent vasodepressor activity in experimental animals. Specific CNP receptors and gene transcripts have been identified in human vascular tissues, but the bioactivity and metabolism of CNP in humans are unknown. Accordingly, we have studied the renal, hormonal, and hemodynamic responses in nine normal men (seated, nonfasting) receiving a morning infusion (2 h) of synthetic human CNP-22 (5 pmol/kg.min) or placebo in single blind, random order. To determine the vasodepressor action, the effect of a second identical (afternoon) infusion on the pressor and hormone responses to angiotensin-II (2, 4, and 8 ng/kg.min each for 30 min) was also studied. In the morning infusion, plasma CNP increased from undetectable baseline levels to plateau levels (mean, 60 +/- 6 pmol/L) at 30-120 min. The mean MCR was 4.8 +/- 0.7 L/min, and the t 1/2 (plasma) was 2.6 min. Compared with the effects of placebo, there were significant increases in plasma cGMP (P = 0.001) and plasma atrial natriuretic peptide (ANP; P = 0.02) and a significant decrease in plasma aldosterone (P = 0.007). No significant hemodynamic action or natriuresis was observed. During coinfusion of angiotensin-II, the expected pressor and aldosterone responses were not significantly altered by CNP. In contrast to atrial and brain natriuretic peptide, short term infusion of CNP in humans, achieving supraphysiological levels in plasma, are not vasodepressor or natriuretic. Increases in plasma ANP and plasma cGMP and inhibition of aldosterone may be due in part to competitive displacement by CNP of ANP in common degradative pathways.
Hunt
P J
PJ
Department of Endocrinology and Cardiology, Christchurch Hospital, New Zealand.
Richards
A M
AM
Espiner
E A
EA
Nicholls
M G
MG
Yandle
T G
TG
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D006152:Cyclic GMP / Q000097:blood* / Q000652:urine; D004837:Epinephrine / Q000097:blood; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D011188:Potassium / Q000652:urine; D012016:Reference Values; D016037:Single-Blind Method; D012964:Sodium / Q000652:urine; D013997:Time Factors
D006728:Hormones; D009419:Nerve Tissue Proteins; D000804:Angiotensin II; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D012964:Sodium; D003404:Creatinine; D006152:Cyclic GMP; D011188:Potassium; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine