The attenuated effect of ATP-sensitive K+ channel opener pinacidil on renal haemodynamics 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 the 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 hypertensive rats (SHR) and in normotensive controls (Wistar Kyoto, WKY). Since pinacidil reduced blood pressure significantly in both groups, the abdominal aorta was clamped before pinacidil administration to yield a renal perfusion pressure equivalent to that during pinacidil infusion. Pinacidil significantly decreased renal vascular resistance in both groups, but the relative change from baseline value was greater in WKY than in SHR. These effects of pinacidil were abolished by pretreatment with glibenclamide (3 mg/kg body wt i.v.). Proximal tubular stop-flow pressure (Psf), an index of glomerular capillary pressure, was significantly elevated by pinacidil infusion in WKY, a response abolished by pretreatment with glibenclamide, but not in SHR. The tubuloglomerular feedback response of Psf was not affected by pinacidil in either group. These data suggest that the activity of K(ATP) channels in SHR may be attenuated in the renal microvasculature. This may contribute to the elevated vascular tone in the renal preglomerular vasculature in SHR.
Mimuro
T
T
Department of Medicine, Kidney Center, Tokyo Women's Medical College, Japan.
Kawata
T
T
Onuki
T
T
Hashimoto
S
S
Tsuchiya
K
K
Nihei
H
H
Koike
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D020110:Pinacidil / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011677:Punctures; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D020110:Pinacidil; D005905:Glyburide