CALCIUM-CHANNEL BLOCKERS BLUNT POSTURAL CUTANEOUS VASOCONSTRICTION INHYPERTENSIVE PATIENTS

The aim of this work was to test whether calcium channel blockers inte rfere with skin vasoconstrictor reflexes that minimize postural increa ses in capillary pressure and avoid fluid extravasation and eventually subcutaneous edema. Studies were conducted in 23 untreated mild to mo derate essential hypertensives; drugs, either calcium channel blockers or not, were given for 2 weeks according to a crossover, sequence-ran domized design. Skin brood flow was measured by laser Doppler flowmetr y in two skin areas: (I)the dorsum of the foot, where arteriovenous an astomoses are poorly represented, and (2) the plantar surface of the g reat toe, where those anastomoses are predominant. Determinations were obtained both with the foot at heart level and with it placed passive ly 50 cm below the heart level; percent flow changes from the horizont al to the dependent position were the measure of postural vasoconstric tion. Two dihydropyridine derivatives, amlodipine (10 mg UID) and nife dipine (60 mg UID), and verapamil (240 mg BID), a chemically unrelated compound, diminished to similar extents the postural fall in skin blo od flow at the dorsum of the foot. Blockade of alpha(1)-adrenergic and AT-1 subtype angiotensin LI receptors by doxazosin (4 mg UID) and los artan (50 mg UID), respectively, exerted no effect. Postural skin bloo d flow responses at the plantar surface of the great toe were unmodifi ed during the pharmacological trials. Thus, calcium channel blockers o f different chemical origins antagonized postural skin vasoconstrictio n at the dorsum of the foot. The data indicate altered postural capill ary blood flow regulation, since arteriovenous anastomoses are anatomi cally absent at this site; the effect was independent of either alpha( 1)-adrenoceptor or angiotensin II receptor antagonism. Interference wi th skin postural vasoconstrictor mechanisms may result in net filtrati on of fluid to the extravascular compartment. This mechanism might exp lain the as yet unknown pathogenesis of ankle edema during treatment w ith calcium antagonists.