Selective reserpine-induced supersensitivity of the positive inotropic and chronotropic responses to isoprenaline and salbutamol in guinea-pig isolated atria.
1 Dose-response curves for the positive inotropic and chronotropic responses to isoprenaline were obtained in atria from untreated guinea-pigs and those receiving various reserpine pretreatments. 2 Tension responses were unaffected, whereas rate responses were depressed by the lowest dose of reserpine (0.05 mg/kg i.p. at 24 hours). 3 With larger 24 h doses and a 3 day pretreatment, the rate and tension dose-response curves were progressively displaced to the left, indicating supersensitivity which was greater for tension at each pretreatment. 4 No supersensitivity to histamine or Ca2+ could be detected, leading to the conclusion that it was selective for the beta-adrenoceptor agonists possibly at the receptor level. 5 As an indication of the adrenergic neurone depleting effectiveness of each reserpine dosage, preparations were exposed to test doses of beta-phenylethylamine. 6 Salbutamol was a partial agonist in untreated atria, the maximum rate (63.3%) and tension (10.0%) responses being less than those for isoprenaline. In atria from reserpine pretreated animals the supersensitivity was revealed as an increase of this maximum compared with isoprenaline. 7 The significance of this observation in relation to the possible mechanism of the supersensitivity is discussed.
D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology*; D013268:Stimulation, Chemical
D010627:Phenethylamines; D006632:Histamine; D012110:Reserpine; D007545:Isoproterenol; D000420:Albuterol; D002118:Calcium