EFFECT OF CALCIUM-CHANNEL BLOCKADE ON SKIN BLOOD-FLOW IN DIABETIC HYPERTENSION - A COMPARISON OF ISRADIPINE AND ATENOLOL

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 co rrelates with the presence of diabetic retinopathy and proteinuria. Th ey speculated that it might be possible to reverse this decrease in bl ood flow by using agents with peripheral vasodilating properties. They chose the calcium channel blocking agent isradipine as a prototype. A s a contrast agent, they chose atenolol, which has an equivalent antih ypertensive effect but minimal peripheral vasodilating properties. The y studied 24 diabetic hypertensive patients in a randomized, two-way c rossover design. They assigned patients randomly to one or the other a ctive drug and titrated to a maximum tolerated maintenance dose. Skin blood flow was measured at the end of the titration and maintenance ph ases. Patients then entered a four-week washout period, followed by cr ossover to the alternative drug, and measurements were repeated. At ba seline, the twenty-four-hour mean ambulatory systolic blood pressure w as 150 +/- 2 mm Hg with a twenty-four-hour mean diastolic blood pressu re 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, nonhypertensive patients. The re was no difference in skin blood flow between the two, groups at bas al skin temperature or at a controlled temperature of 35 degrees C. Bo th atenolol and isradipine successfully lowered blood pressure in the study patients. There was a slightly greater decrease in systolic bloo d pressure with isradipine and a greater decrease in heart rate with a tenolol. Neither isradipine nor atenolol treatment affected skin blood flow values at the maximal 44 degrees C temperature. However, at basa l skin temperature and at 35 degrees C, isradipine-treated patients ha d substantial increases in skin blood flow at NUTR sites. For example, skin blood flow at the knee at 35 degrees 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 control s (all P<0.01). The authors found a twofold to threefold increase in b asal skin blood flow at NUTR sites with isradipine treatment. This deg ree of increase is substantially greater than that previously demonstr ated by their group using pentoxifylline. Locally reduced skin blood f low is a factor in promoting skin breakdown and delayed healing. Furth er study is needed to explore the possibility that isradipine treatmen t may enhance healing of diabetic skin ulcers.