title: Reassessment of the blocking activity of prazosin at low and high concentrations on sympathetic neurotransmission in the isolated mesenteric vasculature of rats.
abstract: 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.
authors.affiliation: Department of Pharmacology, Miyazaki Medical College, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Yamamoto
authors.forename: W H
authors.initials: WH
authors.lastname: Cline
authors.forename: K
authors.initials: K
authors.lastname: Takasaki
mesh_terms: 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
chemical_list: D015016:Yohimbine; D000255:Adenosine Triphosphate; D009638:Norepinephrine; D011224:Prazosin