Heterogeneous effect of calcium antagonists on leg oedema

AIMS: To compare the effect of amlodipine, a prototype dihydropyridine calcium-channel blocker with lercanidipine, a newer dihydropyridine compound with lipophilic properties, on dependent oedema generation and interference with skin blood flow vasomotion in hypertensive patients. DESIGN: Single-blind, sequence-randomized, cross-over comparison of amlodipine and lercanidipine. Drugs were given at equipotent doses (10 mg daily and 20 mg daily, respectively) in 22 never-treated mild-to-moderate hypertensive men (age: 48 +/- 5 years). Each treatment was administered for 2 weeks with a 2-week intervening period to restore baseline values. MAIN OUTCOME MEASURES: Dependent oedema formation was quantified through leg weight changes (water displacement method). Blood pressure (the mean of at least 10 determinations) was recorded by an automated oscillometric device and skin blood flow (laser Doppler flowmetry) measured at the dorsum of the foot, both supine and with the limb passively placed 50 cm below the heart level, to evaluate the behaviour of cutaneous postural vasoconstriction, an autoregulatory mechanism that minimizes gravitational increases in capillary pressure and avoids fluid extravasation when standing. RESULTS: Leg weight was increased by both drugs, but the increase was significantly greater during treatment with amlodipine than with lercanidipine. Blood pressure decreased to a similar extent and postural vasoconstriction was antagonized comparably during both treatments. CONCLUSIONS: The oedema-forming potential of amlodipine is greater than that induced by lercanidipine, a difference which emerged in the presence of a comparable drop in blood pressure and could not be attributed to interference with postural vasoconstrictor mechanisms.