title: Alpha 1-adrenoceptor subtypes mediating adrenergic vasoconstriction in kidney, one-clip Goldblatt and deoxycorticosterone acetate-salt hypertensive rats.
abstract: We characterised the functional alpha 1-adrenoceptors involved in mediating adrenergic vasoconstrictor responses in kidney of two-kidney one-clip (2K1C) Goldblatt and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In sodium pentobarbital-anaesthetised rats, frequency- and dose-dependent renal vasoconstrictor responses were obtained by direct electrical renal nerve stimulation, close renal arterial administration of phenylephrine (PE), and methoxamine. Administration of amlodipine, a dihydropyridine calcium channel antagonist (bolus dose of 200 and 400 micrograms/kg and an infusion of 50 and 100 micrograms/kg/h, respectively) and the alpha 1-adrenoceptor antagonist 5-methylurapidil (5 micrograms/kg plus 1.25 micrograms/kg/h and twice this dose) suppressed renal nerve-, PE-, and methoxamine-induced vasoconstrictions 14-70% (p < 0.05-0.001) in 2K1C Goldblatt and DOCA-salt hypertensive rats. The alpha 1B-adrenoceptor alkylating agent, chloroethylclonidine (5 micrograms/kg plus 1.25 micrograms/kg/h and twice this dose) caused significant attenuation (p < 0.001) of renal nerve-induced vasoconstriction by 19-23% in DOCA-salt hypertensive rats but did not affect PE- and methoxamine-induced vasoconstriction in either 2K1C Goldblatt or DOCA-salt hypertensive rats. In contrast, in 2K1C Goldblatt rats vasoconstrictor responses were potentiated by renal nerve stimulation and methoxamine. The data show that the functional renal postjunctional alpha 1-adrenoceptors on the vasculature of both hypertensive models are primarily of the alpha 1A-subtype, as reflected by their sensitivity to amlodipine and 5-methylurapidil. Moreover, an interaction appears to occur between the alpha 1-adrenoceptor subtypes at renal vessels in 2K1C Goldblatt hypertensive rats.
authors.affiliation: Department of Physiology, Medical School, Birmingham, England.
authors.forename: M
authors.initials: M
authors.lastname: Abdul Sattar
authors.forename: E J
authors.initials: EJ
authors.lastname: Johns
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003900:Desoxycorticosterone / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; C057446:5-methylurapidil; D017311:Amlodipine; D010656:Phenylephrine; C051731:chlorethylclonidine; D003900:Desoxycorticosterone; D008729:Methoxamine; D003000:Clonidine