The K(ATP) channel opener nicorandil: effect on renal hemodynamics in spontaneously hypertensive and Wistar Kyoto rats.
Adenosine triphosphate-sensitive K channels (K(ATP)) may subserve vasodilation in the renal microvasculature. Using micropuncture techniques, we examined whether the renal vasomotor action of K(ATP) differs in hypertensive and normotensive animals. Nicorandil (NC), a K(ATP) opener, was given i.v. (1 mg/hr/kg) to spontaneously hypertensive rats (SHR) or Wistar Kyoto rats (WKY). Mean arterial blood pressure decreased in both groups. Renal blood flow was almost unchanged in SHR but increased significantly in WKY. This effect was completely abolished by pretreatment with glibenclamide (GC; 3 mg/kg i.v.). To investigate the effect of NC on the regulatory mechanism of renal microcirculation, we measured proximal tubular stop-flow pressure (SFP) and assessed tubuloglomerular feedback (TGF) by monitoring SFP during loop perfusion with artificial tubular fluid. NC significantly increased SFP in WKY, an effect abolished by pretreatment with GC. In SHR, however, treatment with NC elicited no significant change in SFP. TGF response was not affected by NC treatment in either group. The data suggest that K(ATP) may modulate preglomerular vascular resistance, especially in the larger vascular segments not subject to TGF regulation, and may be attenuated in SHR. This might, at least in part, be attributable to the increased vascular resistance in SHR.
Kawata
T
T
Department of Internal Medicine II, School of Medicine, Hokkaido University, Sapporo, Japan.
Mimuro
T
T
Onuki
T
T
Tsuchiya
K
K
Nihei
H
H
Koike
T
T
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D006977:Hypertension, Renal / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000737:chemistry; D007684:Kidney Tubules / Q000098:blood supply / Q000737:chemistry; D020108:Nicorandil / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; D020108:Nicorandil; D000255:Adenosine Triphosphate