RT Journal Article
SR Electronic
T1 Inhibitory effect of alpha-1 adrenoceptor stimulation on cardiac sympathetic neurotransmission in pithed normotensive rats.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 500
OP 504
VO 236
IS 2
A1 de Jonge, A
A1 van den Berg, G
A1 Qian, J Q
A1 Wilffert, B
A1 Thoolen, M J
A1 Timmermans, P B
A1 van Zwieten, P A
YR 1986
UL http://jpet.aspetjournals.org/content/236/2/500.abstract
AB In the present study we investigated the inhibitory effect of the selective alpha-1 adrenoceptor agonists cirazoline, amidephrine and St 587 on the cardiac sympathetic neurotransmission in pithed normotensive rats. Increases in heart rate were elicited by electrical stimulation of the cardiac sympathetic nerves or by i.v. administration of norepinephrine, isoproterenol or tyramine. Intravenous pretreatment of the animals with cirazoline, amidephrine or St 587 diminished the heart rate response to sympathetic stimulation significantly. However, the tachycardia produced by norepinephrine, isoproterenol or tyramine was also inhibited significantly by the selective alpha-1 adrenoceptor agonists. The selective alpha-1 antagonist prazosin blocked the sympathoinhibitory effect to alpha-1 adrenoceptor stimulation significantly. However, the inhibitory effect of cirazoline and St 587 was not suppressed completely by a maximally effective dose of prazosin. In contrast, the sympathoinhibitory action of amidephrine was antagonized completely by prazosin. However, the selective alpha-2 antagonist rauwolscine also produced a significant, albeit modest, attenuation of the sympathoinhibitory effect to amidephrine. The results of the present study indicate that alpha-1 adrenoceptor agonists, at relatively high doses, inhibit the sympathetic neurotransmission in rat heart. This sympathoinhibitory effect is mediated largely by alpha-1 adrenoceptors which are localized postjunctionally rather than prejunctionally.