Mechanical response of rat myocardium to dibutyryl cyclic AMP in relation to effects of alpha-and beta-adrenoceptor stimulators.
Dibutyryl cyclic AMP, and alpha- and beta-adrenoceptor stimulators are all able to elicit inotropic effects. alpha- and beta-Adrenoceptor stimulation are known to change each myocardial contraction-relaxation cycle differently. In order to elucidate the myocardial function of cyclic AMP the effects of dibutyryl cyclic AMP on the contraction-relaxation cycle of isolated rat heart papillary muscle were examined and compared to the effects of alpha-and beta-adrenoceptor stimulation, respectively. Dibutyryl cyclic AMP (in the presence of propranolol) increased developed tension (Tmax) by 18%, rate of tension rise (T'max) by 46%, rate of tension fall (T'min) by 62% and onset-rate of relaxation (T"min) by 136%. These changes in the contraction-relaxation cycle were strikingly similar to those produced by isoprenaline (beta-adrenoceptor stimulation). The response to dibutyryl cyclic AMP, however, developed much more slowly than did the response to isoprenaline. The latter effect was associated with cyclic AMP elevation in a way indicating a trigger function for cyclic AMP. The alpha-adrenoceptor stimulation (by phenylephrine combined with propranolol), however, increased measures both for contraction and for relaxation by about the same degree, and the effects occurred without changes of cyclic AMP contents. Phenylephrine alone (combined alpha-and beta-adrenoceptor stimulation) elicited a substantial cyclic AMP elevation but gave mechanical effects only slightly different from the pure alpha-adrenergic response. Thus cyclic AMP effects did not seem to be fully expressed in this case. As a whole, the results indicate that the effects of both dibutyryl cyclic AMP and of isoprenaline are mediated by the cyclic AMP-system while alpha-adrenoceptor stimulation involves other mechanisms.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000032:analysis; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D010656:Phenylephrine; D003994:Bucladesine; D011433:Propranolol; D000242:Cyclic AMP