title: Evidence for an alpha 1-adrenoceptor subtype mediating adrenergic vasoconstriction in Wistar normotensive and stroke-prone spontaneously hypertensive rat kidney.
abstract: We wished to characterise the alpha 1-adrenoceptor subtypes mediating renal vasoconstrictor responses in pentobarbital anaesthetised normotensive rats and stroke-prone spontaneously hypertensive rats (SPSHR). Renal nerve stimulation, close renal arterial administration of phenylephrine (PE, a mixed alpha 1a- and alpha 1b-adrenoceptor agonist) and methoxamine (a putative alpha 1a-adrenoceptor agonist) resulted in frequency and dose-dependent renal vasoconstrictor responses. Both dihydropyridine calcium channel antagonist amlodipine (200 micrograms kg-1 plus 50 micrograms kg-1 h-1 and twice this dose) and the alpha 1a-adrenoceptor antagonist 5-methylurapidil (5 micrograms kg-1 plus 1.25 micrograms kg-1 h-1 and twice this dose) suppressed renal nerve-, PE-, and methoxamine-induced vasoconstrictions by between 21 and 59% (p < 0.05-0.001) in normotensive rats and SPSHR. The alpha 1b-adrenoceptor alkylating agonist chloroethylclonidine (5 micrograms kg-1 plus 1.25 micrograms kg-1 h-1 and twice this dose) attenuated renal nerve-mediated vasoconstrictions by 20% (p < 0.01), but not those induced by PE and methoxamine. This pattern of agonist and blocking drug interaction suggests that the renal postjunctional alpha 1-adrenoceptors require extracellular calcium and are sensitive to 5-methylurapidil, characteristics of the alpha 1a-adrenoceptor subtype. Moreover, a similar situation exists at the renal resistance vessels of SPSHR.
authors.affiliation: Department of Physiology, Medical School, Birmingham, England.
authors.forename: M A
authors.initials: MA
authors.lastname: Sattar
authors.forename: E J
authors.initials: EJ
authors.lastname: Johns
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000503:physiopathology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; D017311:Amlodipine; D010656:Phenylephrine; C051731:chlorethylclonidine; D008729:Methoxamine; D003000:Clonidine