PERIPHERAL EDEMA FORMATION WITH LACIDIPIN E, NITRENDIPINE AND NIFEDIPINE IN SPONTANEOUSLY HYPERTENSIVE RATS

Introduction : Clinical studies suggest that lacidipine (LA) is better tolerated than other DHP, in terms of peripheral edema. We evaluated edema due to LA, nitrendipine (NT) and nifedipine (NF) in SHR. Methods : Mean arterial pressure (MAP) was measured with an intra-femoral pro be. Peripheral edema was determined (i) by the plasmatic distribution of 14C-albumin, (ii) by Evans blue extravasation. Results : In bolus(i p), LA, NT and NF had non different effects oil plasmatic ALB, i.e. 3,9 +/- 1,7 (DELTA % vs control at 60 min mean +/- SEM, n = 18). Evan s blue extravasation (hind paws muscle = EBM) was positively correlate d to MAP reduction (EBM = 0,1 x AMAP + 5,2 ; p < 0,025), without diffe rences between the molecules. In chronical administration (9 days), at comparable MAP decrases (31 +/- 2 mmHg), there was less edema formati on with LA (0,05 mg/kg/j) than with NT (0,5 mg/kg/j) or NF (1,4 mg/kg/ j) : the variations of ALB were respectively (% vs control at 45 min after tracer injection ; mean +/- SD) : + 5 % (n = 10) vs. 73 % (n = 1 4; p < 0,01 vs LA) and + 34 % (n = 10; p < 0,01 vs LA); no significant change of hematocrit or plasma volume was noted. Conclusion : Our res ults confirm, in SHR, that lacidipine induces a very moderate edema fo rmation. This does not seem to be due to a renal effect, nor to an eff ect on peripheral resistances. It was only observed in chronical admin istration, which suggests that pharmacokinetic properties of lacidipin e are involved.