Cyclic AMP in myocytes isolated from hypertrophied rat hearts.
Impaired inotropic responsiveness to isoproterenol stimulation has been reported in the hypertrophied hearts of spontaneously hypertensive rats and renal hypertensive rats. This study was carried out in order to investigate the possibility that a defect in cyclic AMP production by cardiac myocytes is responsible for the impaired inotropic responsiveness of these hearts. Basal and isoproterenol stimulated cyclic AMP levels were measured in ventricular myocytes isolated from hypertrophied rat hearts. Cyclic AMP accumulation was also measured in the presence of isobutyl-methyl-xanthine, a phosphodiesterase inhibitor, and the results were compared to the appropriate controls. In the spontaneously hypertensive rat, no changes were detected in the basal or isoproterenol stimulated cyclic AMP formation. This suggests that the biochemical alterations leading to a diminished inotropic response in this model of cardiac hypertrophy involve abnormalities in mechanisms other than cyclic AMP production. In the renal hypertensive rat, basal and isoproterenol stimulated cyclic AMP levels were significantly depressed as compared to controls. This suggests that abnormalities in the signal transduction mechanism and formation of cyclic AMP are, at least in part, responsible for the impaired inotropic responsiveness seen in this model. These results confirm that cardiac hypertrophy is a heterogeneous process. Reduced inotropic responsiveness to isoproterenol stimulation in the hypertrophied hearts of the SHR and the RHR, both models of pressure overload hypertrophy, involve different biochemical alterations. Results of this study suggest that the physiologic response of cardiac hypertrophy may not be as important as the underlying cause of hypertrophic stimuli in determining the pathophysiological consequences.
Hilal-Dandan
R
R
Department of Heart and Hypertension Research, Cleveland Clinic Foundation, Ohio.
Khairallah
P A
PA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium