SHORT-TERM AND LONG-TERM INHIBITION OF ENDOGENOUS ATRIAL-NATRIURETIC-PEPTIDE IN DOGS WITH EARLY-STAGE HEART-FAILURE

Citation
D. Fukai et al., SHORT-TERM AND LONG-TERM INHIBITION OF ENDOGENOUS ATRIAL-NATRIURETIC-PEPTIDE IN DOGS WITH EARLY-STAGE HEART-FAILURE, Japanese Circulation Journal, 62(8), 1998, pp. 604-610
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Peripheal Vascular Diseas
ISSN journal
0047-1828
Volume
62
Issue
8
Year of publication
1998
Pages
604 - 610
Database
ISI
SICI code
0047-1828(1998)62:8<604:SALIOE>2.0.ZU;2-D
Abstract
Early-stage heart failure (HF) is characterized by an increase in circ ulating atrial natriuretic peptide (ANP) without activation of the ren in-angiotensin-aldosterone system (RAAS) or body fluid retention. To t est the hypothesis that elevated endogenous ANP suppresses the RAAS, m aintains body fluid balance, and regulates vascular tone in early-stag e HF, we assessed the effects of short-term. and long-term inhibition of ANP on cardiorenal and neurohormonal functions. Short-term antagoni sm was produced by bolus administration (3 mg/kg) of HS-142-1, an anta gonist of guanylate-cyclase coupled ANP receptors, and long-term antag onism was produced by continuous infusion (1 mg/kg per h) of HS-142-1 for 8 h to dogs with early-stage HF induced by rapid ventricular pacin g (270 beats/min, 8 days). In this experimentally produced HF, plasma ANP was significantly increased relative to the pre-pacing value, hut not plasma renin activity (PRA) or plasma aldosterone level. HS-142-1 significantly suppressed plasma and urinary guanasine 3',5'-cyclic mon ophosphate (cGMP) levels, markers of endogenous ANP activity, in both experiments. Although mean arterial pressure and cardiac output did no t change significantly, pulmonary capillary wedge pressure and right a trial pressure were elevated in both experiments. While short-term inh ibition of ANP did not change PRA and aldosterone levels, long-term in hibition significantly increased these hormonal levels, resulting in d ecreases in urine flow rate, urinary sodium excretion rate, glomerular filtration rate, and renal plasma flow. These findings suggest that e ndogenous ANP plays a critical role in regulating venovascular tone, i nhibiting activation of RAAS, and maintaining renal functions in early -stage HF.