EXTRACELLULAR ATP IN THE REGULATION OF RENAL MICROVASCULAR FUNCTION

Considerable attention has been focused on the purine nucleoside, aden osine, in the control of renal blood flow, epithelial transport, and r enin secretion; however, surprisingly little attention has been direct ed toward the renal effects of purine nucleotides such as adenosine tr iphosphate (ATP). Recent studies utilizing in vivo micropuncture and i n vitro techniques have demonstrated that renal vascular, epithelial, and mesangial cells respond to extracellular ATP via mechanisms distin ct from those elicited by adenosine. ATP vasoconstricts afferent but n ot efferent arterioles whereas adenosine vasoconstricts both vascular segments. Adenosine-mediated afferent arteriolar vasoconstriction is a bolished by adenosine receptor antagonists, whereas the response to AT P is enhanced. ATP-mediated vasoconstriction reaches a maximum within seconds of exposure while the vasoconstriction induced by adenosine de velops more slowly L-type calcium channel antagonists such as diltiaze m or felodipine prevent the sustained afferent vasoconstriction produc ed by ATP. Data from micropuncture experiments indicate that peritubul ar capillary infusion of ATP reduces glomerular pressure and results i n marked attenuation of the tubuloglomerular feedback mechanism, which transmits signals from the macula densa to the afferent arteriole. Th ese data support the existence of ATP-sensitive P-2 purinoceptors in t he preglomerular microvasculature that contribute to the control of re nal vascular function via activation of calcium channels.