This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McMahon, E. G. Articles by Cook, C. S. Search for Related Content PubMed PubMed Citation Articles by McMahon, E. G. Articles by Cook, C. S. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Blood Pressure Medicines Diets

(Hypertension. 1995;26:95-100.)
© 1995 American Heart Association, Inc.

Articles

Effects of SC-56525, a Potent, Orally Active Renin Inhibitor, in Salt-Depleted and Renal Hypertensive Dogs

Ellen G. McMahon; Po-Chang Yang; Maribeth A. Babler; Stephen E. Bittner; Osman D. Suleymanov; Kimberly J. Cain-Janicki; Louis J. Bedell; Gunnar J. Hanson; Chyung S. Cook

From GD Searle & Co, Skokie, Ill, and St Louis, Mo.

Abstract SC-56525 is a nanomolar inhibitor of plasma renin activity in human, cynomolgus monkey, dog, guinea pig, Yucatan micropig, and rabbit but is less active in rat. The oral bioavailability of SC-56525 in conscious dogs at doses of 5 mg/kg IV and 30 mg/kg PO was 66.1±16.4%. Oral dosing with SC-56525 at 3, 10, and 30 mg/kg in salt-depleted dogs induced a dose-dependent reduction in mean arterial pressure and inhibition of plasma renin activity with no significant effect on heart rate. In two-kidney, one clip renal hypertensive dogs, SC-56525 given orally at 10, 30, and 60 mg/kg daily for 4 days lowered blood pressure significantly. In conscious dogs monitored in their home cages via radiotelemetry, no significant changes in heart rate occurred in response to large drops in blood pressure in both renal hypertensive and salt-depleted dogs with the renin inhibitor SC-56525. SC-56525 is a nanomolar, orally active inhibitor of renin and effectively lowers blood pressure in both salt-depleted and renal hypertensive dogs.

Key Words: renin • sodium, dietary • hypertension, renovascular • dogs • renin-angiotensin system

This article has been cited by other articles:

				Y. Bukhtiyarov, M. Zecher, R. Panemangalore, Z. Wu, J. G. Bruno, J. Yuan, Z. Xu, L. W. Dillard, G. M. McGeehan, R. K. Harrison, et al. Cloning, Characterization and Site-Directed Mutagenesis of Canine Renin J. Biochem., December 1, 2007; 142(6): 671 - 680. [Abstract] [Full Text] [PDF]