Involvement of alpha1B-adrenoceptors in the positive inotropic effect of endogenous noradrenaline in rabbit myocardium.
We studied the alpha1-adrenoceptor subtypes mediating the positive inotropic effects of phenylephrine and noradrenaline as well as endogenous noradrenaline released by tyramine in rabbit papillary muscle. In the presence of propranolol, both phenylephrine and tyramine produced a positive inotropic effect in a concentration-dependent manner. WB4101 (N-[2-(2,6-dimethoxyphenoxy]ethyl]-2,3-dihydro-1,4-benzodioxin+ ++-2-methanamine) and chlorethylclonidine each antagonized the positive inotropic effect of phenylephrine. On the other hand, only chlorethylclonidine significantly blocked the positive inotropic effect of tyramine. However, the presence of both antagonists was needed to block the positive inotropic effect elicited by the exogenous addition of the low concentration of noradrenaline. These data suggest that after extensive blockade of beta-adrenoceptors the positive inotropic effects of phenylephrine and exogenous noradrenaline result from stimulation of the alpha1A- and alpha1B-adrenoceptor subtypes, whereas that of endogenous noradrenaline is mediated via the alpha1B-adrenoceptor subtype. This could be explained by assuming that the alpha1B-adrenoceptor subtype population may be located on a space confronting more closely to the sympathetic nerve endings than the alpha1A-adrenoceptor subtype population.
Hattori
Y
Y
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Kanno
M
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D014439:Tyramine / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; C051731:chlorethylclonidine; D011433:Propranolol; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D009638:Norepinephrine; D014439:Tyramine