Abstract
We studied the α 1-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 β-adrenoceptors the positive inotropic effects of phenylephrine and exogenous noradrenaline result from stimulation of the α 1A and α 1B-adrenoceptor subtypes, whereas that of endogenous noradrenaline is mediated via the α 1B-adrenoceptor subtype. This could be explained by assuming that the α 1B-adrenoceptor subtype population may be located on a space confronting more closely to the sympathetic nerve endings than the α 1A-adrenoceptor subtype population.
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