Nitric Oxide Synthase, But Not Heme Oxygenase, Mediates The Adenosine A2B Receptor‐Sensitive Renal Vasodilations In Female Rats

Abstract

Stimulation of adenosine receptors by 5′‐N‐ethylcarboxamidoadenosine (NECA) dilates the renal vasculature. Studies were conducted in phenylephrine‐preconstricted isolated perfused kidneys of female rats to determine: (i) the relative contributions of adenosine receptor subtypes to NECA responses and (ii) the potential modulation of these responses by nitric oxide synthase (NOS) and/or heme oxygenase (HO). Cumulative bolus injections of NECA (1.6–50 nmol) elicited dose‐related vasodilations. NECA responses were attenuated after blockade of A2B (alloxazine) but not A2A [8‐(3‐Chlorostyryl) caffeine] or A3 (VUF 5574) receptors, suggesting preferential involvement of A2B receptors in NECA vasodilations. NOS activation appears to mediate the A2B‐dependent NECA response because: (i) NOS inhibition by L‐NAME attenuated NECA responses, (ii) no additional inhibition of NECA responses occurred upon concurrent exposure to L‐NAME and alloxazine, and (iii) L‐arginine abrogated the alloxazine‐evoked inhibition of NECA responses. Conversely, HO inhibition by zinc protoporphyrin affected neither NECA responses nor the attenuating effect of alloxazine on these responses. Overall, the activation of A2B/NOS signaling underlies the vasodilatory effect of NECA in female kidneys.This project was supported financially by the Science and Technology Development Fund (STDF), Egypt, Grant No. 502.