Peer-Reviewed Journal Details
Mandatory Fields
Abdul Sattar M, Johns EJ;
Journal of Cardiovascular Pharmacology
Alpha 1-adrenoceptor subtypes mediating adrenergic vasoconstriction in kidney, one-clip Goldblatt and deoxycorticosterone acetate-salt hypertensive rats.
Optional Fields
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.
Grant Details