Effects of prolonged infusions of atrial natriuretic peptide and isoproterenol on the mechanical and endocrine function of isolated atria.
We have measured the rate of release of atrial natriuretic peptide in response to stretch and to isoproterenol from superfused atria isolated from rats after chronic in vivo infusion of either atrial natriuretic peptide or isoproterenol. The infusion lasted seven days, using minipumps filled with: 1) saline; 2) synthetic atrial natriuretic peptide to release 3 micrograms/kg/h; 3) l-isoproterenol HCl to release 400 micrograms/kg/h. Infusion of isoproterenol caused hypertrophy of the left chambers of the heart, a decrease of atrial content of atrial peptide with increased plasma levels. Infusion of atrial natriuretic peptide resulted only in elevated plasma levels of the peptide. Atria from animals infused with atrial natriuretic peptide responded to stretch and to isoproterenol (10(-9) M) with a prompt and transient release of peptide. Atria from animals infused with isoproterenol showed a severe reduction in sensitivity to the inotropic and chronotropic action of the drug. Their basal release of atrial peptide was extremely reduced and they were unable to respond to stretch or to isoproterenol. These data indicate that high circulating levels of atrial natriuretic peptide do not influence the release of the peptide from the atria, while high levels of isoproterenol drastically reduce it. Beta adrenoceptor desensitization, atrial hypertrophy and decrease of stores of atrial peptide are likely to account for this phenomenon.
Agnoletti
G
G
Cattedra di Cardiologia, Università degli Studi di Brescia, Italy.
Panzali
A F
AF
Cornacchiari
A
A
De Giuli
F
F
Ferrari
R
R
D000818:Animals; D016275:Atrial Function / Q000187:drug effects*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006332:Cardiomegaly / Q000503:physiopathology; D005089:Exocytosis; D006325:Heart Atria / Q000378:metabolism*; D006333:Heart Failure / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009320:Atrial Natriuretic Factor; D007545:Isoproterenol