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 micrograms/kg per h following a bolus dose of 10 micrograms/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-flow pressure (
SFP), an index of glomerular capillary pressure (Pgc), induced by loop of Henle perfusion was significantly less with
efonidipine treatment (6.7 +/- 1.0% of
SFP with no loop flow) than in control (23.8 +/- 3.1%). In the presence of
efonidipine,
SFP at half-maximal reduction (SFP1/2max), which approximates Pgc at the in vivo steady state tubular flow 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 Pgc remain unaltered and that a marked reduction in
proteinuria is achieved without changes in single nephron GFR or Pgc of superficial nephrons.