THE ATTENUATED EFFECT OF ATP-SENSITIVE K+ CHANNEL OPENER PINACIDIL ONRENAL HEMODYNAMICS IN SPONTANEOUSLY HYPERTENSIVE RATS

In hypertension, impairment of hyperpolarization by K+ efflux through ATP-sensitive K+ (K-ATP) channels may contribute to the elevated renal vascular resistance. To elucidate such a role for K-ATP channels in t he renal vasculature, we used micropuncture techniques to examine the effect of K-ATP channel opener, pinacidil (0.15 mg/h per kg body wt i. v.), on renal and glomerular haemodynamics in spontaneously hypertensi ve rats (SHR) and in normotensive controls (Wistar Kyoto, WKY). Since pinacidil reduced blood pressure significantly in both groups, the abd ominal aorta was clamped before pinacidil administration to yield a re nal perfusion pressure equivalent to that during pinacidil infusion. P inacidil significantly decreased renal vascular resistance in both gro ups, but the relative change from baseline value was greater in WKY th an in SHR. These effects of pinacidil were abolished by pretreatment w ith glibenclamide (3 mg/kg body wt i.v.). Proximal tubular stop-flow p ressure (P-sf), an index of glomerular capillary pressure, was signifi cantly elevated by pinacidil infusion in WKY, a response abolished by pretreatment with glibenclamide, but not in SHR. The tubuloglomerular feedback response of P-sf was not affected by pinacidil in either grou p. These data suggest that the activity of K-ATP channels in SHR may b e attenuated in the renal microvasculature. This may contribute to the elevated vascular tone in the renal preglomerular vasculature in SHR. (C) 1998 Elsevier Science B.V. All rights reserved.