Adenosine is generated within the renal medulla under hypoxic conditions and is known to induce net vasoconstriction within the renal cortex while increasing medullary blood flow and oxygenation. To test the hypothesis that vasoconstriction of outer medullary descending vasa recta (OMDVR) is modulated by adenosine, we examined the effects of adenosine and adenosine A 1 and A 2 receptor subtype agonists on in vitro perfused control and preconstricted rat OMDVR. Constriction with angiotensin II (ANG II, 10 Ϫ 9 M) was attenuated by adenosine in a concentration-dependent manner (EC 50 to 10 Ϫ 5 M) elicited a biphasic response. Additionally, cyclohexyladenosine (10 Ϫ 6 M) caused vasoconstriction and CGS-21680 (10 Ϫ 6 M) had no effect on untreated vessels. Finally, an influence of ANG II receptor stimulation on adenosine A 1 receptor-mediated vasoconstriction could not be shown. These data suggest that OMDVR possess both A 1 and A 2 adenosine receptors and that they mediate constriction and dilatation, respectively. We conclude that adenosine is a potent modulator of OMDVR vasomotor tone and that its net effect is dependent upon local concentrations. ( J. Clin. Invest. 1996. 98:18-23.)

Adenosine has a multitude of functions in the kidney, including vasoregulation of the renal vasculature. The actions of adenosine are mediated by its binding to specific receptors. Four adenosine-receptor subtypes have been cloned and sequenced, the A1, A2a, A2b, and the A3. In this study, the expression of individual adenosine-receptor subtype RNAs in outer medullary descending vasa recta (OMDVR) was investigated. Total RNA isolated from the outer medulla and microdissected, permeabilized OMDVR were subjected to reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for each of the adenosine-receptor subtypes. Subtype-specific probes were used to verify the PCR products by Southern hybridization. Our studies, performed in triplicate on five different rats, indicate the presence of A1, A2a, and A2b adenosine-receptor subtype mRNAs. These products were not attributable to extraneous RNA contamination from other tissue sources, nor did they result from genomic DNA amplification. These data are consistent with pharmacological evaluations, favor A1, A2a, and A2b adenosine-receptor subtype expression in OMDVR, and support a role for adenosine in the regulation of medullary blood flow.

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