Reassessment of the blocking activity of prazosin at low and high concentrations on sympathetic neurotransmission in the isolated mesenteric vasculature of rats.
1. The overflow of endogenous noradrenaline from the rat mesenteric arterial vasculature was determined along with the perfusion pressure response to periarterial nerve stimulation (PNS) (4-12 Hz). 2. The PNS-induced pressor responses were blocked by prazosin at 3 X 10(-8) M but not by prazosin at 10(-6) M or the combination of prazosin at 3 X 10(-8) M and yohimbine (10(-7) M). 3. The PNS-induced overflow of endogenous noradrenaline was significantly augmented by prazosin at 10(-6) M or the combination of prazosin at 3 X 10(-8) M and yohimbine (10(-7) M) but not by prazosin at 3 x 10(-8) M alone. 4. The PNS-induced pressor response and endogenous noradrenaline overflow, in the absence of prazosin, were not significantly influenced by alpha, beta-methylene-adenosine triphosphate (alpha, beta-methylene ATP) (3 X 10(-6) M). The pressor responses to PNS which remained after prazosin at 10(-6) M were abolished by pretreatment with alpha, beta-methylene ATP and therefore attributable to coreleased ATP. 5. The pressor responses to exogenous noradrenaline were abolished by prazosin at both 3 X 10(-8) M and 10(-6) M. 6. These results suggest that no functionally significant amount of ATP was coreleased with noradrenaline by PNS in the presence of prazosin at low concentrations which blocked only postjunctional alpha 1-adrenoreceptors. 7. Thus, these results indicate that the effects of prazosin at high concentrations, such as 10(-6) M, on sympathetic neurotransmission should not be ignored when considering the mechanisms of vasoconstrictor responses to PNS following high concentrations of prazosin.
Yamamoto
R
R
Department of Pharmacology, Miyazaki Medical College, Japan.
Cline
W H
WH
Takasaki
K
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D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D001340:Autonomic Nerve Block; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000294:innervation; D009638:Norepinephrine / Q000097:blood; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*; D014661:Vasoconstriction; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D000255:Adenosine Triphosphate; D009638:Norepinephrine; D011224:Prazosin