Differential inhibiton of alpha-1 and alpha-2 adrenoceptor-mediated pressor responses in pithed rats
Yamaguchi, I.; Kopin, I.J.
Journal of Pharmacology and Experimental Therapeutics 214(2): 275-281
1980
ISSN/ISBN: 0022-3565 PMID: 6104724 Document Number: 157350
The relative potencies of .alpha. adrenoceptor antagonists at pre- and postsynaptic receptors were assessed by comparing their effects on increments in plasma norepinephrine levels and blood pressure during stimulation of the sympathetic outflow from the spinal cord of pithed rats. Since increments in blood pressure are related to the logarithms of increases in plasma norepinephrine, the latter appear to reflect levels of the catecholamine at vascular .alpha. receptors. Phenoxybenzamine, dibenamine and chlorpromazine blocked preferentially postsynaptic .alpha. receptors; phentolamine and tolazoline were nearly equipotent at pre- and postsynaptic receptors and mianserin and piperoxan were more potent inhibitors of presynaptic .alpha. receptors. Phenoxybenzamine and dibenamine were much more effective in blocking the pressor responses to sympathetic stimulation than administered norepinephrine. The opposite was true of mianserin and piperoxan, but phentolamine appeared to be about equipotent in blocking the pressor responses to stimulation and norepinephrine. The pressor effects of administered norepinephrine is mediated by different receptors (.alpha.-2-type) than is the pressor response to stimulation of the sympathetic outflow which appears to be mediated by .alpha.-1-type adrenoceptors.