Mechanism of adenosine receptor-induced renal vasoconstriction in rats

Abstract

Adenosine analogues selective for the A1 subclass of adenosine receptors, such as N6-cyclohexyladenosine (CHA), induce vasoconstriction in the isolated rat kidney perfused at constant flow. Presumably, the vasoconstriction is mediated by increased Ca2+ concentration in renal vascular smooth muscle cells, but the mechanism by which A1 adenosine receptor occupation leads to increased Ca2+ is unknown. In the present experiments, the isolated, perfused rat kidney vasoconstricted in response to CHA, to K depolarization, and to BAY K 8644 (a Ca2+ channel agonist). All of these responses were completely blocked by methoxyverapamil, which suggests that CHA, like K depolarization and BAY K 8644, induces renal vasoconstriction by increasing Ca2+ influx through potential operated Ca2+ channels. The mechanism of action of CHA was different, however, in that pertussis toxin treatment blocked the response to CHA without affecting the responses to K depolarization or to BAY K 8644. Therefore, a pertussis toxin-sensitive step must intervene between occupation of A1 adenosine receptors on renal vascular smooth muscle cells and increased Ca2+ influx through potential-operated Ca2+ channels.