Effects of lemildipine, a new calcium channel blocker, on renal microcirculation in SHR.
The effects of lemildipine, a new dihydropyridine calcium channel blocker, on renal hemodynamics and the tubuloglomerular feedback (TGF) mechanism were examined in anesthetized 9- to 10-wk-old spontaneously hypertensive rats (SHR). Lemildipine, 3 micrograms.kg-1 i.v., did not reduce mean blood pressure (MBP) but tended to increase GFR and increased urinary excretion of sodium (UNaV). Filtration fraction (FF) and fractional excretion of sodium (FENa) remained unaltered. An additional dose of lemildipine, 9 micrograms.kg-1 i.v., reduced MBP and renal vascular resistance. Renal plasma flow tended to increase, and GFR was unchanged. FF significantly fell. UNaV and FENa remained at the control level. Micropuncture experiments revealed that the maximal reduction in proximal stop-flow pressure (SFP), an index of glomerular capillary hydrostatic pressure (Pgc), induced by perfusion of the loop of Henle was significantly reduced by high-dose treatment (8.8 +/- 1.3 vs. 13.7 +/- 1.9 mmHg in control). A high dose of lemildipine induced a rightward and slightly upward shift of the TGF curve; the steady-state tubular flow rate (V1/2) was increased, the maximal slope of the curve decreased, and SFP at V1/2 unaltered. A low dose of lemildipine did not affect TGF response. These results indicate that lemildipine attenuates the TGF response in SHR by dilating afferent arterioles and thereby corrects the left and downward shift of the TGF curve in SHR. In addition, the fall in FF indicates lemildipine-induced efferent arteriolar vasodilatation. Through balanced systemic and glomerular vasodilatation, lemildipine maintains the levels of Pgc and GFR in the face of reduced renal perfusion pressure.
Kawabata
M
M
Fourth Department of Internal Medicine, Shimane Medical University, Izumo, Japan.
Ogawa
T
T
Takabatake
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology; D008138:Loop of Henle; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C038806:1,4-dihydropyridine