Biological actions and pharmacokinetics of C-type natriuretic peptide in conscious sheep.
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.
Department of Endocrinology, Christchurch Hospital, New Zealand.
C J
CJ
Charles
E A
EA
Espiner
A M
AM
Richards
M G
MG
Nicholls
T G
TG
Yandle
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003243:Consciousness; D003404:Creatinine / Q000378:metabolism; D006152:Cyclic GMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008657:Metabolic Clearance Rate; D020098:Natriuretic Peptide, C-Type; D011188:Potassium / Q000652:urine; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D012964:Sodium / Q000652:urine; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D006728:Hormones; D011506:Proteins; D000804:Angiotensin II; D020098:Natriuretic Peptide, C-Type; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; D003404:Creatinine; D006152:Cyclic GMP; D011188:Potassium; D006854:Hydrocortisone