Captopril enhances renal responsiveness to ANF in dogs with compensated high-output heart failure

Abstract

The systemic hemodynamic, hormonal, and renal effects of chronic angiotensin-converting enzyme inhibition (CEI) with captopril and the responses to synthetic atrial natriuretic factor (ANF) infusions in the presence and absence of captopril were examined in normal dogs (n = 6) and in dogs with an arteriovenous (AV) fistula and compensated high-output heart failure (n = 6). This experimental model is characterized by normalization of the circulating renin-angiotensin-aldosterone system (RAAS) and persistent elevations in central filling pressures and plasma ANF. In both normal and AV-fistula dogs, oral captopril for 1 wk at 35 mg.kg-1.day-1 in three divided doses produced progressive reductions in arterial and atrial pressures (P less than 0.05), plasma ANF (P less than 0.05), and aldosterone (P less than 0.05). After 1-2 days of a modest increase in urinary sodium excretion (UNaV) (P less than 0.05), all of the dogs regained and maintained sodium balance during captopril administration. On the 8th day of the captopril regimen, synthetic ANF was infused at 15 and 30 ng.kg-1.min-1 for 75-min periods each. Control infusion experiments were performed in the same animals before captopril administration. The normal dogs exhibited dose-related elevations in UNaV (P less than 0.05) that were not augmented with captopril (P greater than 0.05). In contrast, in the AV-fistula dogs the observed renal unresponsiveness to synthetic ANF in the control experiments was reversed with chronic CEI, and ANF-induced UNaV achieved levels comparable to those obtained in the normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril Reduces Interstitial Renal Fibrosis and Preserves More Normal Renal Tubules in Neonatal Dogs with Partial Urethral Obstruction: A Preliminary Study

“…In addition, it should be noted that some researchers rely on volume fraction changes to calculate the amount of scar tissue or other histological parameters. Concerning the changes in the total values of the threedimensional structures, it is essential to multiply the densities by the total volume of the reference volume (here the kidney) [7][8][9] . The densities are just ratios that do not allow any conclusion about changes in the total amount of structures.…”

“…The peritoneum, fascia and skin were closed using chromic and nylon [6] . After the operation the dogs were divided into two groups: the first (experimental group) was treated with captopril, 35 mg/kg/day, dissolved in drinking water, for 6 weeks [7] . The second (positive control) group received an equal volume of water.…”

Acute Natriuretic Effect of Fasidotrilat, a Mixed Inhibitor of Neutral Endopeptidase and Angiotensin I-Converting Enzyme, in Rats with Heart Failure

“…An attenuation of the natriuretic effect of exogenous ANF has been reported in experimental and clinical heart failure [3], and an explanation may be that the activation 292 Pharmacology 1998;56:291- 296 Marie/Mossiat/Lecomte/Bralet of the renin-angiotensin system antagonizes the ANF effect. Indeed, in rats with aortocaval fistula or myocardial infarction, pretreatment with an angiotensin I-converting enzyme (ACE) inhibitor or with losartan led to restoration of the natriuretic effect of exogenous ANF [4][5][6][7][8].…”

El síndrome cardiorenal en insuficiencia cardíaca: Un paradigma en evolución

“…Los mecanismos que contribuyen a este fenómeno incluyen una disminución relativa de la secreción dichos péptidos natriuréticos 12,13 , una mayor resistencia renal a su efecto, secundaria a la gran hiperactividad del SRAA y del sistema simpático, al efecto aumentado de la Endopeptidasa Neutra EC 3.4.24.11 , que degrada estos péptidos 18 , a la modulación negativa de los receptores NPR-A y la disminución de la presión de perfusión y del flujo arterial renal. En este sentido, dada su de relevancia clínica, es importante hacer notar que el bloqueo efectivo del SRAA puede restablecer el efecto de los péptidos natriuréticos, como lo sugieren estudios en modelos animales de insuficiencia cardíaca, en los cuales la inhibición de la enzima de conversión de angiotensina con Captopril, mejora la natriuresis y la diuresis inducida por la infusión de ANP exógeno 19 ( figura 2).…”