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[Do renal vascular D2 receptors exist?]
M Barthelmebs1, J P Krieger, M Grima
1Institut de pharmacologie, URA DO589 CNRS, Université Louis-Pasteur et service d'hypertension artérielle et maladies vasculaires, CHRU, Strasbourg.
Abstract:
Two dopamine receptors are present on the renal vasculature: post-synaptic D1-receptors and neuronal D2-receptors. The existence of postsynaptic vascular D2-receptors is now under discussion. The aim of this study was to characterize in vitro the renal vascular response to bromocriptine, a D2 preferential agonist. Bromocriptine (10(-7) to 3.10(-5) M) induced a concentration dependent relaxation (EC50 = 1.4 +/- 0.1 x 10(-6) M, m +/- SEM, n = 5) on the isolated perfused rat kidney whose vascular tone had been previously increased by 25% with prostaglandin F2 alpha and adrenoceptors blocked (phenoxybenzamine 10(-5) M, sotalol 10(-5) M). Response to bromocriptine was comparable to that induced by dopamine on terms of EC50 and Emax (87 +/- 3% reversion of the increase in renal vascular resistance induced by prostaglandin F2 alpha). Nevertheless, unlike response to dopamine, bromocriptine-induced relaxation was not antagonized by the selective D1-receptor antagonist, SCH 23390 (3 x 10(-9) M) but was inhibited by selective D2-receptor antagonists, domperidone (10(-8) M) and DO 710 (3 x 10(-8) M). To account for renal vasodilatation, an interaction of bromocriptine with 5-HT receptors was excluded. Indeed, neither 8-OHDPAT, 5-methoxytryptamine nor 5-HT were able to induce any renal vasodilatation on the isolated perfused rat kidney and domperidone is devoid of antagonist activity on 5-HT receptors. The present results suggest that bromocriptine-induced vasodilatation on the rat renal vascular bed was linked to an interaction with vascular postsynaptic D2-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)