Microvascular mechanisms involved in calcium antagonist edema formation.

The effects of calcium antagonists on microcirculation in cat skeletal muscle were studied using a plethysmographic technique. Nifedipine given locally intraarterially decreased vascular resistance in a dose-dependent way by means of vasodilatation that was relatively more pronounced in precapillary vessels than in postcapillary vessels. This led to an increase in capillary hydrostatic pressure, which was the main force for the concomitant transcapillary fluid filtration from blood to tissue. Capillary filtration coefficient, which reflects precapillary sphincter tone (and thus the capillary surface area available for fluid exchange) and specific capillary permeability, was not changed much by nifedipine, even when vasodilatation was pronounced. A comparison of five different calcium antagonists (diltiazem, felodipine, nifedipine, nimodipine, and verapamil) showed that at the same degree of vasodilatation these agents caused the same increase in capillary hydrostatic pressure and the same net transcapillary fluid transfer, but caused no change in capillary filtration coefficient. Nifedipine also interfered with local vascular control in the tissue, leading to an impairment of "autoregulation of capillary hydrostatic pressure" at variations in arterial blood pressure and an impairment of protection against increased hydrostatic load in dependent vascular beds. It is concluded that peripheral edema (usually ankle edema) during treatment with calcium antagonists may result from vasodilatation alone and an inhibition of local vascular (myogenic) control.