Impaired venoarteriolar reflex as a possible cause for nifedipine-induced ankle oedema

Ankle oedema is not an uncommon side effect of treatment with nifedipine. To evaluate the possible effect of nifedipine on the microcirculation of the skin, 18 patients with systemic hypertension who were known to develop ankle oedema after nifedipine and 19 patients with systemic hypertension who did not develop ankle oedema after nifedipine were studied. Following four weeks of nifedipine therapy (10 mg, three times daily), the microcirculation on the dorsum of the foot was measured using laser-Doppler flowmetry. Estimation of the microcapillary flow was made both after supine resting and on standing upright. The venoarteriolar reflex was expressed as the standing flow in percentage of the resting flow. There was no significant difference between the two groups of patients in the resting flow, supine flow, or the venoarteriolar reflex before nifedipine therapy (P greater than 0.4). Before nifedipine, the blood blow in the skin of both groups of patients was reduced from the supine level upon standing, thus indicating a normal response to dependency. After nifedipine administration, no significant difference was observed between the two groups of patients in the resting flow (P greater than 0.5). The flow on standing, however, was 96.2% of that measured during resting supine in patients who developed ankle oedema and 79.8% of the resting flow in the patients who did not develop ankle oedema, suggesting a weaker venoarteriolar reflex in patients who developed ankle oedema following administration of nifedipine (P less than 0.0001). Thus, the microcapillary flow did not decrease upon standing in patients who developed ankle oedema following nifedipine therapy, indicating an abnormal venoarteriolar reflex. This may explain why ankle oedema develops in such patients following nifedipine.