Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney

Abstract

The effects of rat atrial tissue extract on renal hemodynamics and fluid and electrolyte excretion were investigated in the isolated perfused rat kidney (IK). IK were perfused at a constant effective perfusion pressure of about 90 mmHg. After control clearance periods (C), extracts of rat atria (AE) or ventricles (VE) were added to the perfusate and three 10-min experimental periods followed. AE, but not VE, significantly increased (P less than 0.001) renal vascular resistance (RVR) to 133 +/- 8% of C, GFR to 201 +/- 34%, filtration fraction to 245 +/- 41%, urine flow (V) to 675 +/- 131%, fractional excretion (FE) of H2O to 336 +/- 29%, absolute Na excretion (UNaV) to 1,259 +/- 290%, FENa to 642 +/- 129%, UKV to 2,226 +/- 1,237%, and FEK to 542 +/- 119%. Despite the marked natriuresis, since GFR doubled, Na reabsorption rose from 78.3 +/- 36.3 in C to 132 +/- 36.3 mueq/min after AE. The effects of AE were immediate and lasted to the end of the perfusion. The lower the initial control GFR, the larger was the AE-induced increase in GFR. Perfusion with low [Ca] (0.2 mM) or verapamil (10(-5) M) severely blunted the hemodynamic, diuretic, kaliuretic, and natriuretic effects of AE. AE decreased rather than increased the RVR when IK were perfused with vasoconstrictors such as angiotensin II, norepinephrine, or vasopressin. The results demonstrate that AE acts directly on the kidney, eliciting powerful Ca-dependent hemodynamic and natriuretic responses. The natriuresis induced by AE can be accounted for, at least in part, by its renal hemodynamic effects rather than by the presence of a putative tubular natriuretic factor. The hypothesis is advanced that AE contains a substance(s) which behaves as a functional agonist/antagonist of endogenous vasoconstrictors with a preferential site of action on the efferent arterioles of the renal vasculature.

The Diuretic Effect of Calcium Entry Blockade in Normals and Hypertensive Patients.

“…5, nitrendipine enhanced the natriuretic effect of ANF markedly. This finding contrasts with observations in the isolated perfused kidney, where nifedipine abolished the renal vasodilatory effect of ANF (Camargo et al 1984). However, enhanced ANFinduced natriuresis has also been found in anesthetized rabbits treated with nitrendipine, as was reported recently by Seino et al (1988).…”

Inhibition of atrial natriuretic peptide-induced natriuresis by plasma hydrolysates containing pepsanurin.

“…In the isolated kidney, inhibition of ANP by pepsanurin was also observed in the absence of major hemodynamic changes. As described, 13 ANP increased perfusion pressure in vasodilated preparations, but the subsequent inhibition of ANP by pepsanurin was not associated with a decrease in this parameter. We cannot preclude, however, that the inhibition of ANP by pepsanurin could be mediated by subtle changes in intrarenal hemodynamics and peritubular forces, which have been recognized as important determinants for the action of this hormone.…”

Enalapril attenuates natriuresis of atrial natriuretic factor in humans.

“…In the isolated kidney preconstriction with angiotensin n was shown to enhance the vasodilator and natriuretic effects of ANF. 2 In contrast, the natriuretic response to ANF is attenuated in conditions accompanied by a stimulated renin-angiotensin system, such as low sodium intake 10 '" or heart failure. 12 ' l3 This emphasizes the importance of other circulatory factors, such as arterial pressure.…”

“…Studies in perfused, isolated kidneys have shown that the vasodilator and natriuretic actions of ANF are enhanced by preconstriction with substances such as norepinephrine and angiotensin II and reduced when vasoconstriction is impaired with a calcium entry blocker. 2 This finding led to the idea that the vasorelaxant effect of ANF concerns antagonism of the prevalent vasoconstrictive activity.…”