BIOLOGICAL ACTIONS AND PHARMACOKINETICS OF C-TYPE NATRIURETIC PEPTIDEIN CONSCIOUS SHEEP

C-type natriuretic peptide (CNP) is found in abundance in neural tissu e and in endothelial cells of vascular tissue, where it may participat e in the regulation of vascular tone. However, few studies have examin ed the metabolism and systemic actions of CNP in conscious animals. Ac cordingly, we investigated the hemodynamic, renal, and hormonal effect s 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 raise d from a mean baseline level of 2-3 pmol/l (detection limit) to platea u at 10 +/- 1.2 and 115 +/- 18 pmol/l during doses 1 and 10, respectiv ely. 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 infus ion 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. S imilar 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 significant ly affecting arterial pressure. CNP may play an important role in the regulation of regional hemodynamics and fluid homeostasis.