Microcirculatory effects of KATP channel blockade by sulphonylurea derivatives in humans

Abstract

Background Recent investigations have shown that glibenclamide inhibits the opening of vascular ATP‐sensitive potassium channels during ischemia. This observation may implicate cardiovascular effects of sulphonylurea derivatives when used under conditions of ischemia in patients with Type 2 diabetes mellitus. In addition to resistance arteries, the (pre) capillary vessels also contain ATP‐dependent potassium channels. Closure of these channels by sulphonylurea derivatives might affect the development of microvascular disease in Type 2 diabetes mellitus. Therefore, we investigated the microcirculatory effects of sulphonylurea derivatives in Type 2 diabetic patients as compared with healthy volunteers. Materials and methods Arteriovenous blood flow (skin temperature and laser Doppler flux) and capillary blood cell velocity were measured before and during infusion of four doses of glibenclamide (0·1, 0·3, 1·0 and 3·0 µg min⁻¹ dL⁻¹) into the brachial artery of 14 Type 2 diabetic patients and 13 healthy controls. The experiments included appropriate time control studies. Results Both skin temperature and laser Doppler flux decreased in response to glibenclamide in healthy volunteers (−7 ± 2%, P < 0·0005 and −31 ± 11%, P = 0·001, respectively), but did not change in Type 2 diabetic patients (1 ± 3%, P = 0·29 and 4 ± 14%, P = 0·97). However, capillary blood cell velocity decreased in Type 2 diabetic patients (−38 ± 18%, P = 0·04), but did not change in healthy volunteers (−1 ± 11%, P = 0·28). Conclusions The results of the present study indicate that glibenclamide indeed affects microvascular blood flow. Glibenclamide may induce redistribution of the microvascular skin flow from nutritive flow to arteriovenous shunt flow in Type 2 diabetic patients. Therefore, closure of ATP‐dependent potassium channels by glibenclamide possibly plays a role in the development of microangiopathy in Type 2 diabetic patients.