AJP - Regulatory, Integrative and Comparative Physiology, Vol 268, Issue 1 201-R207, Copyright © 1995 by American Physiological Society
Biological actions and pharmacokinetics of C-type natriuretic peptide in conscious sheep
C. J. Charles, E. A. Espiner, A. M. Richards, M. G. Nicholls and T. G. Yandle
Department of Endocrinology, Christchurch Hospital, New Zealand.
C-type natriuretic peptide (CNP) is found in abundance in neural tissue and
in endothelial cells of vascular tissue, where it may participate in the
regulation of vascular tone. However, few studies have examined the
metabolism and systemic actions of CNP in conscious animals. Accordingly,
we investigated the hemodynamic, renal, and hormonal effects of intravenous
CNP-22 administered at two doses (1 and 10 pmol.kg-1.min-1 as dose 1 and
dose 10, respectively) in a vehicle-controlled study in normal conscious
sheep (n = 8). Plasma CNP levels were raised from a mean baseline level of
2-3 pmol/l (detection limit) to plateau at 10 +/- 1.2 and 115 +/- 18 pmol/l
during doses 1 and 10, respectively. Metabolic clearance rates were 3.15
+/- 0.39 and 2.48 +/- 0.36 l/min, respectively. The plasma half-life of CNP
on termination of infusion was rapid (1.6 +/- 0.27 min). Dose 10 increased
plasma guanosine 3',5'-cyclic monophosphate (P = 0.0002), reduced cardiac
output by 18% (P = 0.01), but did not significantly affect mean arterial
pressure. Similar suppression (15%) of cardiac output occurred during dose
1 (P = 0.078). Both doses were natriuretic. This study demonstrates that
CNP is natriuretic in sheep and lowers cardiac output without significantly
affecting arterial pressure. CNP may play an important role in the
regulation of regional hemodynamics and fluid homeostasis.
