Inhibitory effect of aldosterone on the natriuretic response to atrial natriuretic peptide in hypocapnic rats.
1. Previous studies have shown that acute hypocapnia blunts the natriuretic effect of atrial natriuretic peptide (ANP) independently of the renal nerves and that the effect of ANP is restored by total adrenalectomy. We investigated the natriuretic response to ANP in potassium canrenoate (aldosterone receptor antagonist)-treated rats to clarify whether aldosterone contributes to the attenuated natriuretic response to ANP during hypocapnia. 2. Wistar rats, challenged with either canrenoate or saline vehicle, were infused with 10 micrograms/kg per h ANP during acute hypocapnia achieved by mechanical ventilation. 3. In saline-treated hypocapnic rats, ANP infusion failed to increase the fractional excretion of sodium (FENa) (from 3.49 +/- 0.26 to 5.03 +/- 0.42%, respectively; n = 6) which was similar to values for time control rats (from 3.00 +/- 0.61 to 4.41 +/- 0.68%; n = 6). The hyporesponsiveness to ANP during hypocapnia was also evident when the FENa was compared with that of normocapnic rats (from 3.92 +/- 0.69 to 7.87 +/- 0.45%; P < 0.05; n = 6). In canrenoate-treated rats, ANP infusion caused greater increases in sodium excretion (FENA from 3.05 +/- 0.71 to 7.21 +/- 0.45%; P < 0.05; n = 8) than saline infusion (FENA from 4.16 +/- 1.11 to 5.47 +/- 0.66%; n = 6), despite the hypocapnia. The increase in FENA after ANP infusion during hypocapnia (4.16 +/- 0.86%) was similar to the increase seen during normocapnia (3.89 +/- 0.86%; n = 9). 4.


CONCLUSIONS
(i) acute hypocapnia blunts the natriuretic effects of ANP; and (ii) this attenuation is restored by potassium canrenoate treatment. The data suggest that aldosterone plays an important role by limiting the renal actions of ANP during acute hypocapnia.
Department of Surgery, University of Tokyo, Japan.
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Kanauchi
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Mimura
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001784:Blood Gas Analysis; D002191:Canrenoic Acid / Q000494:pharmacology; D016857:Hypocapnia / Q000503:physiopathology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine
D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D002191:Canrenoic Acid; D012964:Sodium