ACTIVITE PRO-OEDEMATEUSE DE LA LACIDIPINE, DE LA NITRENDIPINE ET DE LA NIFEDIPINE CHEZ LE RAT SPONTANEMENT HYPERTENDU

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 probe. Peripheral edema was determined (i) by the plasmatic distribution of 14C-albumin, (ii) by Evans blue extravasation. Results: In bolus(ip), LA, NT and NF had non different effects on plasmatic *ALB, i.e. + 3,9 ± 1,7 (Δ% vs control at 60 min; mean ± SEM, n = 18). Evans blue extravasation (hind paws muscle = EBM) was positively correlated to MAP reduction (EBM = 0,1 x ΔMAP + 5,2; p <0,025), without differences between the molecules. In chronical administration (9 days), at comparable MAP decrases (31 ± 2 mmHg), there was less edema formation 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 = 14; 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 results confirm, in SHR, that lacidipine induces a very moderate edema formation. This does not seem to be due to a renal effect, nor to an effect on peripheral resistances. It was only observed in chronical administration, which suggests that pharmacokinetic properties of lacidipine are involved.