Effect of Calcium Channel Blockade on Skin Blood Flow in Diabetic Hypertension: A Comparison of Isradipine and Atenolol

Abstract

In previous studies, using laser Doppler techniques, the authors have demonstrated a duration-dependent reduction in skin blood flow reserve at sites of nutritive (NUTR) perfusion that occurs in diabetes and correlates with the presence of diabetic retinopathy and proteinuria. They speculated that it might be possible to reverse this decrease in blood flow by using agents with peripheral vasodilating properties. They chose the calcium channel blocking agent isradipine as a prototype. As a contrast agent, they chose atenolol, which has an equivalent antihypertensive effect but minimal peripheral vasodi lating properties. They studied 24 diabetic hypertensive patients in a randomized, two-way crossover design. They assigned patients randomly to one or the other active drug and titrated to a maximum tolerated maintenance dose. Skin blood flow was measured at the end of the titration and maintenance phases. Patients then entered a four-week washout period, followed by crossover to the alternative drug, and measurements were repeated. At baseline, the twenty-four-hour mean ambulatory systolic blood pressure was 150 ±2 mm Hg with a twenty-four-hour mean diastolic blood pressure of 93 ±1 mm Hg. Thermally stimulated skin blood flow reserve was about 50% lower in these patients as compared with an age-, sex-, and weight-matched group of 28 nondiabetic, nonhyper tensive patients. There was no difference in skin blood flow between the two groups at basal skin temperature or at a controlled temperature of 35°C. Both atenolol and isradipine successfully lowered blood pressure in the study patients. There was a slightly greater decrease in systolic blood pressure with isradipine and a greater decrease in heart rate with atenolol. Neither isradipine nor atenolol treatment affected skin blood flow values at the maximal 44°C temperature. However, at basal skin temperature and at 35°C, isradipine-treated patients had substantial increases in skin blood flow at NUTR sites. For example, skin blood flow at the knee at 35°C with isradipine treatment was 3.1 ±0.4 mL/min/100 g compared with 1.1 ±0.2 with atenolol, 1.3 ±0.1 with placebo, and 0.9 ±0.1 for the nondiabetic controls (all P<0.01). The authors found a twofold to threefold increase in basal skin blood flow at NUTR sites with isradipine treatment. This degree of increase is substantially greater than that previously demonstrated by their group using pentoxifylline. Locally reduced skin blood flow is a factor in promoting skin breakdown and delayed healing. Further study is needed to explore the possibility that isradipine treatment may enhance healing of diabetic skin ulcers.