ALPHA(1)-ADRENOCEPTOR SUBTYPES MEDIATING ADRENERGIC VASOCONSTRICTION IN KIDNEY OF 2 KIDNEY, ONE-CLIP GOLDBLATT AND DEOXYCORTICOSTERONE ACETATE SALT HYPERTENSIVE RATS

We characterised the functional alpha(1)-adrenoceptors involved in med iating adrenergic vasoconstrictor responses in kidney of two-kidney on e-clip (2K1C) Goldblatt and deoxycorticosterone acetate (DOCA)-salt hy pertensive rats. In sodium pentobarbital-anaesthetised rats, frequency - and dose-dependent renal vasoconstrictor responses were obtained by direct electrical renal nerve stimulation, close renal arterial admini stration of phenylephrine (PE), and methoxamine. Administration of aml odipine, a dihydropyridine calcium channel antagonist (bolus dose of 2 00 and 400 mu g/kg and an infusion of 50 and 100 mu g/kg/h, respective ly) and the alpha(1)-adrenoceptor antagonist 5-methylurapidil (5 mu g/ kg plus 1.25 mu g/kg/h and twice this dose) suppressed renal nerve-, P E-, and methoxamine-induced vasoconstrictions 14-70% (p < 0.05-0.001) in 2K1C Goldblatt and DOCA-salt hypertensive rats. The alpha(1B)-adren oceptor alkylating agent, chloroethylclonidine (5 mu g/kg plus 1.25 mu g/kg/h and twice this dose) caused significant attenuation (p < 0.001 ) of renal nerve-induced vasoconstriction by 19-23% in DOCA-salt hyper tensive rats but did not affect PE- and methoxamine-induced vasoconstr iction in either 2K1C Goldblatt or DOCA-salt hypertensive rats. In con trast, in 2K1C Goldblatt rats vasoconstrictor responses were potentiat ed by renal nerve stimulation and methoxamine. The data show that the functional renal postjunctional alpha(1)-adrenoceptors on the vasculat ure 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)-adren oceptor subtypes at renal vessels in 2K1C Goldblatt hypertensive rats.