Effects of a calcium channel blocker, manidipine hydrochloride, on the regulatory mechanism of glomerular capillary pressure in SHR.
In an attempt to clarify whether glomerular capillary pressure (Pgc) in hypertension can be reduced by a calcium channel blocker (CaB), renal clearance and micropuncture experiments were carried out on male heminephrectomized spontaneously hypertensive rats (SHR; n = 15). Renal circulatory parameters (RBF and GFR) and proximal tubular stop flow pressure (Psf) were measured during the control period, during manual aortic clamping, and after administration of manidipine hydrochloride (MDP, 10 micrograms/kg body weight in bolus). Because Psf only represents Pgc during zero tubular flow, the responsiveness of tubulo-glomerular feedback (TG feedback) was also assessed to obtain the "steady state Pgc", an operating point in each experimental period. Administration of MDP decreased systemic blood pressure (SBP) and renal vascular resistance (RVR), but increased renal blood flow (RBF) significantly. Psf decreased following the administration of MDP (33.65 +/- 1.45 mmHg), reaching a lower level than during aortic clamping (39.93 +/- 2.37 mmHg) or in the control period (50.78 +/- 2.73 mmHg). TG feedback responsiveness was attenuated during clamping, and was incompletely inhibited by MDP, whereas the operating point (29.3 mmHg) was lower than during clamping (32.9 mmHg) or in the control period (41.0 mmHg). The stability of RBF during the alteration of renal perfusion pressure (RPP) was not abolished by MDP. From these results, we suggest that MDP significantly decreases Pgc in the steady state not only by the reduction of RPP, but also by the amelioration of renal microcirculation.
Onuki
T
T
Department of Medicine, Tokyo Women's Medical College, Japan.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D004095:Dihydropyridines / Q000494:pharmacology*; D005246:Feedback / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009578:Nitrobenzenes; D010879:Piperazines; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; C054218:manidipine