This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Charles, C. J. Articles by Sybertz, E. J. Search for Related Content PubMed PubMed Citation Articles by Charles, C. J. Articles by Sybertz, E. J.

Hypertension, Vol 17, 643-651, Copyright © 1991 by American Heart Association

ARTICLES

Hemodynamic and hormonal effects of neutral endopeptidase inhibitor SCH 39370 in sheep

CJ Charles, EA Espiner, VA Cameron, AM Richards, TG Yandle and EJ Sybertz
Department of Endocrinology, Princess Margaret Hospital, Christchurch, New Zealand.

Whole body clearance of atrial natriuretic factor is due to both receptor uptake and enzymatic degradation initiated by neutral endopeptidase 24.11. The effects of neutral endopeptidase inhibition have been studied in seven sodium-replete sheep using SCH 39370, a specific and potent inhibitor of neutral endopeptidase, in the presence or absence of exogenous hormone [rat ANF-(101-126), 2.4 pmol/kg/min for 2 hours]. SCH 39370 alone (2.5 mg/kg bolus) increased plasma atrial natriuretic factor and plasma cyclic GMP levels, lowered arterial pressure for periods beyond changes in plasma atrial natriuretic factor or cyclic GMP, and suppressed both plasma aldosterone and cortisol levels when compared with vehicle injections. The effects of SCH 39370 were similar to or exceeded those of atrial natriuretic factor infusions, which induced significantly greater increases in plasma atrial natriuretic factor (p = 0.01). Neither agent alone was natriuretic. When SCH 39370 and atrial natriuretic factor were given together, plasma cyclic GMP but not atrial natriuretic factor levels were increased (p = 0.013) compared with atrial natriuretic factor infusion alone, and the half-life was prolonged (p = 0.002) in the presence of SCH 39370. The hypotensive response was greater than that induced by atrial natriuretic factor alone (p = 0.03) but not different from SCH 39370 alone. Inhibitory effects of SCH 39370 on aldosterone levels were similar in the presence of absence of exogenous atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				M. W. TAAL, V. D. NENOV, W. WONG, S. R. SATYAL, O. SAKHAROVA, J. H. CHOI, J. L. TROY, and B. M. BRENNER Vasopeptidase Inhibition Affords Greater Renoprotection than Angiotensin-Converting Enzyme Inhibition Alone J. Am. Soc. Nephrol., October 1, 2001; 12(10): 2051 - 2059. [Abstract] [Full Text] [PDF]

				C. J. Charles, E. A. Espiner, A. M. Richards, and E. J. Sybertz Endopeptidase Inhibition in Angiotensin-Induced Hypertension : Effect of SCH 39370 in Sheep Hypertension, July 1, 1995; 26(1): 89 - 94. [Abstract] [Full Text]