Altered responsiveness of hypertrophied rat hearts to alpha- and beta-adrenergic stimulation.
Inotropic responsiveness to alpha- and beta-adrenergic agents was examined in pressure-overload hypertrophied rat hearts. Pressure overload was induced in rats by abdominal aortic constriction. Three weeks post-constriction, hearts were isolated and perfused with buffer containing various concentrations of (1) calcium (2) isoproterenol (3) forskolin, or (4) phenylephrine. The change in rate of left ventricular pressure development (delta + dP/dt) with increasing perfusate calcium concentrations was comparable in hypertrophied hearts of aortic-constricted rats (AC) and hearts of sham-operated rats (SO). However, with isoproterenol or forskolin stimulation, inotropic responsiveness (delta + dP/dt) was 50% lower in hypertrophied hearts of AC. This was associated with significantly lower tissue cAMP levels. Beta-adrenoceptor number and affinity were unchanged in the hypertrophied myocardium. Maximum inotropic responsiveness to phenylephrine was also lower in hypertrophied hearts and was associated with reduced alpha-adrenoceptor numbers. The data suggest that altered inotropic responsiveness to alpha-adrenergic stimulation may, in part, be due to reduced cardiac alpha-adrenoceptor density. However, post-receptor mechanisms including alterations in cAMP metabolism may contribute to the reduced responsiveness to beta-adrenergic stimulation in hypertrophied hearts of AC.
Foster
K A
KA
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Hock
C E
CE
Reibel
D K
DK
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology*; D005576:Colforsin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D010656:Phenylephrine; D007545:Isoproterenol; D002118:Calcium