The contribution of the renin-angiotensin system to the natriuretic responses to intrarenal infusions of 1, 5, 25, and 125 pmol/kg/min synthetic rat atrial natriuretic peptide 101-126 was determined in one-kidney anesthetized dogs. In vehicle-treated dogs, atrial natriuretic peptide 101-126 increased fractional sodium excretion from 1.8 ±0.6% to a peak response of 5.1 ±0.9% during infusion of 25 pmol/kg/min. The peptide progressively decreased mean arterial pressure from 110±5to94±4 mm Hg, renal vascular resistance from 0.40 ± 0.02 to 0.30 ± 0.02 mm Hg/ml/min, and arterial plasma renin activity from 4.3 ±1.6 to 3.1 ±0.8 ng/ml/hr. When the renin-angiotensin system was blocked by 3 mg/kg i.v. enalaprilat, baseline pressure fell to 86 ±4 mm Hg, and subsequent infusions of atrial natriuretic peptide 101-126 did not affect fractional sodium excretion. The decreases in blood pressure N umerous studies have demonstrated that atrial natriuretic peptides (ANP) increase sodium excretion, lower mean arterial pressure (MAP), and suppress the renin-angiotensin system in both conscious and anesthetized dogs.1 " 7 Since angiotensin II (ang II) produces vasoconstriction and enhances sodium reabsorption, 8 the depressor and natriuretic effects of ANP may be due in part to the reduction in endogenous renin levels. Such an interaction would be consistent with the observations that, compared with the responses in other hypertensive models, the natriuretic responses 9 and the depressor responses 10 to acute administration of ANP were exaggerated in two-kidney, one-clip hypertensive rats, a model in which renin levels are elevated.In the present study, the renal and systemic responses to intrarenal administration of synthetic rat ANP 101-126 were determined before and after interruption of the renin-angiotensin system by inhibition of angiotensin converting enzyme (ACE) with the acid form of enalapril, MK 422 (enalaprilat), in anesthetized dogs. After ACE inhibition, ang II levels were increased by intravenous infusion of that peptide at a dose that restored blood pressure to control levels. Since intra- venous ang II elevated both renal perfusion pressure and renal vascular resistance, a second group of dogs was studied in which the vasoconstrictor effects of ang II were restricted to the kidney by intrarenal artery infusion of ang II. The responses to ANP 101-126 measured during intrarenal and intravenous ang II administration were compared with those obtained during intrarenal and intravenous infusions of the a-adrenergic agonist, methoxamine (ME). In this way, the contribution of the renin cascade to the biological effects of ANP 101-126 was determined.
Materials and MethodsEighteen female mongrel dogs were anesthetized with vinbarbital (50 mg/kg i.v.) and intubated with a cuffed endotracheal tube. Ventilation with room air was maintained by a respirator (Harvard, South Natick, Massachusetts). Each animal was supported in an upright position, and both kidneys were exposed via bilateral flank incisions. Following unilateral nephre...