Evidence for an alpha 1-adrenoceptor subtype mediating adrenergic vasoconstriction in Wistar normotensive and stroke-prone spontaneously hypertensive rat kidney.

M A Sattar, E J Johns

Department of Physiology, Medical School, Birmingham, England.

Journal of cardiovascular pharmacology 1994 Feb

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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.

Citation

M A Sattar, E J Johns. Evidence for an alpha 1-adrenoceptor subtype mediating adrenergic vasoconstriction in Wistar normotensive and stroke-prone spontaneously hypertensive rat kidney. Journal of cardiovascular pharmacology. 1994 Feb;23(2):232-9