Enhanced atrial peptide natriuresis during angiotensin and aldosterone blockade in dogs.
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.
Bie
P
P
Division of Experimental Medicine, St. Luke's Hospital and Foundation, Kansas City, Missouri 64111.
Wang
B C
BC
Leadley
R J
RJ
Goetz
K L
KL
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000502:physiology*; D004231:Diuresis; D004285:Dogs; D005260:Female; D006439:Hemodynamics; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects*; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood
D000451:Mineralocorticoid Receptor Antagonists; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D012964:Sodium; D012083:Renin; D011188:Potassium