title: Role of alpha-1 and alpha-2 adrenoceptors in the sympathetic control of the proximal urethra.
abstract: In the pithed rat, postjunctional alpha-1 and alpha-2 adrenoceptors mediate increases in proximal urethral perfusion pressure (UPP). The present study examined the role of alpha-1 and alpha-2 adrenoceptors in sympathetic control of the isolated in situ proximal urethra of the rat. An endogenous alpha adrenergic constriction was demonstrated in the proximal urethra by eliciting dose-related and phentolamine-sensitive increases in UPP after the systemic administration of tyramine. Transient dose-related and hexamethonium-sensitive increases in UPP were also elicited by ganglionic stimulation with 1,1-dimethyl-4-phenylpiperazinium (DMPP). Based on the relative sensitivity of the DMPP response to standard autonomic blockers, it was determined that constriction is the predominant autonomic response in the proximal urethra and this response is mediated by alpha adrenoceptor mechanisms. Prazosin, a selective alpha-1 adrenoceptor antagonist, substantially reduced (72%) the steady-state increases in UPP elicited by discrete low frequency electrical stimulation of the spinal hypogastric outflow. In contrast, selective alpha-2 adrenoceptor blockade with rauwolscine significantly increased (28%) the UPP response to hypogastric stimulation. Prazosin also abolished the increase in urethral tone elicited by tyramine, whereas rauwolscine had no effect on the tyramine. A different response profile was observed for prazosin and rauwolscine when the steady-state increase in UPP was evoked by simultaneously stimulating the midthoracic and hypogastric spinal outflow. Under these conditions of sympathoadrenal activation, UPP was reduced by both prazosin and rauwolscine (63 and 50%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, Pennsylvania.
authors.forename: R N
authors.initials: RN
authors.lastname: Willette
authors.forename: C F
authors.initials: CF
authors.lastname: Sauermelch
authors.forename: J P
authors.initials: JP
authors.lastname: Hieble
mesh_terms: D000818:Animals; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014439:Tyramine / Q000494:pharmacology; D014521:Urethra / Q000187:drug effects / Q000294:innervation*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D004246:Dimethylphenylpiperazinium Iodide; D014439:Tyramine; D011224:Prazosin