Renal effects of efonidipine hydrochloride, a new calcium antagonist, in spontaneously hypertensive rats with glomerular injury

1. To obtain some insight into the renoprotective mechanism of the new calcium antagonist efonidipine hydrochloride, we evaluated the acute effects of efonidipine on proteinuria, glomerular haemodynamics and the tubuloglomerular feedback (TGF) mechanism in anaesthetized 24-25-week-old spontaneously hypertensive rats (SHR) with glomerular injury. 2. Efonidipine infusion at 10 mu g/kg per h following a bolus dose of 10 mu g/kg, i.v., reduced systemic blood pressure (BP) and renal vascular resistance, whereas renal plasma flow (RPF), glomerular filtration rate (GFR), filtration fraction, urine volume and urinary sodium excretion were unaltered. Urinary protein excretion was clearly diminished from 163+/-25 to 105+/-24 ng/min per g kidney weight. 3. Micropuncture experiments revealed that the maximal reduction of proximal stop-how pressure (SFP), an index of glomerular capillary pressure (P-gc), induced by loop of Henle perfusion was significantly less with efonidipine treatment (6.7+/-1.0% of SFP with no loop flow) than in central (23.8+/-3.1%). In the presence of efonidipine, SFP at half-maximal reduction (SFP1/2max), which approximates P-gc at the in vivo steady state tubular how rate, remained unchanged compared with control (36.9+/-0.8 vs 35.3+/-0.7 mmHg, respectively) and the slope of dependency on mean BP was not different between control and efonidipine. 4. These results indicate that efonidipine attenuates the TGF response in SHR by dilating the afferent arteriole, thus maintaining the level of RPF and GFR despite reduced renal perfusion pressure. Constant GFR and SFP1/2max under efonidipine suggest that single nephron GFR and P-gc remain unaltered and that a marked reduction in proteinuria is achieved without changes in single nephron GFR or P-gc of superficial nephrons.