Enhanced atrial peptide natriuresis during angiotensin and aldosterone blockade in dogs

Abstract

The hypothesis that the weak natriuretic effect elicited by modest amounts of atrial peptide is mediated via the inhibition of renin and aldosterone was evaluated in the conscious dog. The formation of angiotensin II (ANG II) and the effects of aldosterone (Aldo) were blocked acutely by enalaprilat and canrenoate, respectively. Infusion of alpha-human atrial natriuretic peptide (alpha-hANP) for 2 h at 25 ng.kg-1.min-1 increased plasma atrial peptide concentration 7- to 10-fold. In control experiments, i.e., experiments without ANG II-Aldo blockade, infusion of atrial peptide doubled urine volume (UV) from 0.21 +/- 0.01 to 0.43 +/- 0.09 ml/min and sodium excretion (UNaV) from 18 +/- 5 to 37 +/- 7 mueq/min; mean arterial blood pressure (AP) and atrial pressures decreased, whereas total peripheral resistance increased. The induction of ANG II-Aldo blockade elevated UNaV and UV 10- and 6-fold, respectively, and decreased AP. The subsequent 2-h infusion of atrial peptide elicited a further increase in UNaV (from 195 +/- 28 to 334 +/- 60 mueq/min); the hemodynamic changes were similar to those seen in the absence of ANG II-Aldo blockade, except that AP did not decrease significantly during the administration of atrial peptide. The data demonstrate that pharmacological inhibition of the effects of converting enzyme and Aldo does not impede the natriuretic response elicited by a 7- to 10-fold increase in circulating atrial peptide; in fact, the magnitude of the natriuresis is markedly enhanced during this blockade.

Diuretics

“…8. Similar observations were made for piretanide (Pir, 5pmol/l, lumen) and torasemide (Tor, lOpmol /l , lumen) (a) with increased A TP (less A TP is metabolized in the presence of ouabain) the K+ channel of the luminal membrane is inhibited by ATP WANG et al 1990), (b) increased cytosolic Ca2+, since Ca 2 + is probably exported by an Na+JCa 2 + exchanger, increased Ca 2 + inhibits the K+ channel in the luminal membrane ), (c) cytosolic acidification, since H+ ions are extruded in the TAL by the Na+ JH+ exchanger, ouabain decreases cytosolic pH, and decreased pH inhibits the K+ channel in the luminal membrane ). The effects of ouabain mentioned above can all be explained by its direct effect on the (Na++K+)-ATPase.…”

Volume expansion during NOS substrate donation with l-arginine: regulatory offsetting of renal response?

“…It has been demonstrated, however, that plasma levels of ANP must be increased considerably to provoke an immediate natriuresis (6,8). The present changes of 15% or less appear very small in this context, and the plasma levels of ANP in the two series involving volume expansion were statistically identical.…”

Volume expansion during acute angiotensin II receptor (AT1) blockade and NOS inhibition in conscious dogs

“…However, in the absence of other changes, plasma ANP must be elevated rather substantially to induce an immediate natriuresis (4,6). The present changes appear very small in this context, and the plasma levels of this hormone corresponding to peak sodium excretion in the three series involving volume expansion were identical.…”