NIFEDIPINE INCREASES MICROVASCULAR PERMEABILITY VIA A DIRECT LOCAL EFFECT ON POSTCAPILLARY VENULES

Calcium-channel antagonist drugs are prescribed widely for angina and hypertension. A limiting side effect is edema, which can make heart fa ilure worse. We show that nifedipine, a dihydropyridine-type calcium-c hannel antagonist, can increase vascular permeability in rat skeletal muscle and skin when injected locally. In nifedipine-injected cremaste r muscle, the copper content, used to quantify Monastral blue dye accu mulation, was 15.0 +/- 2.4 mu g/g compared with 5.3 +/- 0.7 mu g/g in control preparations (P < 0.05). The injection of nifedipine in rat sk in in vivo increased local plasma leakage in injected sites from 5.5 /- 1.1 mu l in control sites to 9.9 +/- 2.5, 17.0 +/- 2.4, 24.3 +/- 5. 9, and 23.3 +/- 5.4 mu l in sites injected with 10(-10), 10(-9) 10(-8) , or 10(-7.2) mol/site, respectively (P < 0.05 in each case compared w ith control). Vascular labeling techniques using light microscopy, ele ctron microscopy, and microanalysis show that the microvascular site o f leakage is not from capillaries but from postcapillary venules of 12 -36 mu m in diameter, the same site that controls the edema response i n inflammation. Nifedipine can act within the microcirculation to incr ease the permeability of the postcapillary venule.