Corresponding author: Professor P. Smits, Department of Phar macology, University of Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands Abbreviations: KATP channel, Adenosine-5 '-triphosphate-sen sitive potassium channel; SU, sulphonylurea; FBF, forearm blood flow; SNP, sodium nitroprusside; FVR, forearm vascular resistance; MAP, mean arterial pressure; NIDDM, non-insu lin-dependent diabetes mellitus.

In 1983, Noma [1] was the first to describe that an outward potassium current increased significantly when guinea pig or rabbit cardiac muscle cells were subjected to hypoxia. This current was caused by the activation of potassium channels, which was independent of the intracellular Ca 2+ concentration, but dependent on the intracellular concentration of adenosine-5 ′-triphosphate ([ATP] i ). These so-called ATPsensitive potassium (K ATP ) channels were suggested to play a cardioprotective role during ischaemia. Later, K ATP channels were also found in skeletal muscle [2], smooth muscle [3] and pancreatic beta cells [4] from animals. In pancreatic beta cells the K ATP channels mediate insulin secretion [5] and are a target for sulphonylurea derivatives in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) [6]. Sulphonylurea derivatives are highly specific in blocking pancreatic and cardiovascular K ATP channels, and Diabetologia (1996Diabetologia ( ) 39: 1562Diabetologia ( -1568 Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans Summary Experimental data show that ATP-sensitive potassium (K ATP ) channels not only occur in pancreatic beta cells, but also in the cardiovascular system, where they mediate important cardioprotective mechanisms. Sulphonylurea derivatives can block the cardiovascular K ATP channels and may therefore interfere with these cardioprotective mechanisms. Therefore, it is of clinical importance to investigate whether sulphonylurea derivatives interact with vascular K ATP channels in humans. Using venous-occlusion strain-gauge plethysmography, we investigated whether ischaemia-induced reactive hyperaemia is reduced by the sulphonylurea derivative glibenclamide in 12 healthy male non-smoking volunteers. Forearm vasodilator responses to three periods of arterial occlusion (2, 5 and 13 min) during concomitant infusion of placebo into the brachial artery were compared with responses during concomitant intra-arterial infusion of glibenclamide (0.33A control study (n = 6) showed that time itself did not change the vasodilator response to ischaemia.Glibenclamide significantly increased minimal vascular resistance (from 2.1 ± 0.1 to 2.3 ± 0.2 arbitrary units, Student's t-test: p = 0.01), and reduced mean forearm blood flow (from 37.5 ± 2.0 to 35.4 ± 2.0 ml ⋅ min -1 ⋅ dl -1 after 13 min occlusion, ANOVA with repeated measures: p = 0.006) and flow debt repayment during the first reperfusion minute (ANOVA with repeated measures: p = 0.04). In contrast, total flow debt repayment was not affected. Infusion of glibenclamide into the brachial artery resulted in local concentrations in the clinically relevant range, whereas the systemic concentration remained too low to elicit hypoglycaemic effects. Our results suggest that therapeutic concentrations of glibenclamide induce a slight but significant reduction in the early and peak vasodilation during reactive hyperaemia.

Corresponding author: Professor P. Smits, Department of Phar macology, University of Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands Abbreviations: KATP channel, Adenosine-5 '-triphosphate-sen sitive potassium channel; SU, sulphonylurea; FBF, forearm blood flow; SNP, sodium nitroprusside; FVR, forearm vascular resistance; MAP, mean arterial pressure; NIDDM, non-insu lin-dependent diabetes mellitus.

The reference level for the measurement of blood pressure (BP) is the level of the right atrium. In practice this is regularly disregarded, as the patient's arm is usually placed lower than the right atrial level. The aim of the study was to determine the influence of first, different arm positions and second, different transducer positions on the intra-arterially (i.a.) recorded BP. In 16 healthy men (age 28.1 ± 8.0 (s.d.) years), i.a. BP was recorded at the left arm in supine position, using a 5-7 cm long cannula. The baseline position was with the tip of the cannula placed precisely at the level of the right atrium. Subsequently, the following changes were made: 5, 10, 15 and 20 cm above and 5, 10, 15, and 20 cm below the baseline position. A 2-min rest period was allowed in each position before the BP was measured. The whole procedure was done either with the transducer connected to the arm at the place of the cannula (n ‫؍‬ 7), or with the transducer placed next to the subject and continuously kept at the right atrial level during the BP measurement (n ‫؍‬ 9). Simultaneously, baseline BP was measured indirectly, with a standard mercury sphygmomanometer, in the opposite arm maintained with the cubital fossa at the right atrial level during the whole procedure. This resulted in the first group of

Opening of vascular K(ATP) channels is involved in the forearm vasodilator response to dipyridamole but not to adenosine. Differences in stimulated cell type (endothelium for adenosine versus smooth muscle cells for dipyridamole) may underlie this divergent pharmacologic profile.