DIVERGENT EFFECTS OF DIFFERENT ANTIHYPERTENSIVE DRUGS ON ENDOTHELIUM-DEPENDENT VASODILATION IN THE HUMAN FOREARM

Several studies indicated an abnormal endothelium-dependent vasodilati on (EDV) in hypertensive patients, but no study has systematically inv estigated the effects of different pharmacologic classes of antihypert ensive drugs on EDV. This study aimed to evaluate the effects of three different antihypertensive regimens [angiotensin-converting enzyme (A CE) inhibition, calcium channel blockade, and beta-blockade] on EDV wh en given locally in the forearm at a constant blood pressure. The incr ease in forearm blood flow (FBF) during local intraarterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; ind ucing endothelium-independent vasodilation, EIDV) was measured in youn g, normotensive subjects by venous occlusion plethysmography, before a nd during concomitant local intraarterial infusion of any of the anti hypertensive drugs. Without changing baseline FEE enalaprilat (n = 6, 2.4 mg/h) potentiated the increase in FBF induced by MCh [from 22.6 +/ - 2.3 (SD) to 25.4 +/- 2.3 ml/min/100 mi tissue at 4 mu g/min; p < 0.0 5], but the response to SNP was unchanged. Local intraarterial verapam il infusion (n = 6), at a dose individually titrated to keep baseline FBF unchanged, did not alter the response to MCh infusion, whereas the response to SNP was potentiated. A higher dose of verapamil (n = 6), which increased baseline FBF, increased both EDV and EIDV significantl y in parallel (p < 0.05). The local propranolol infusion (n = 6, 1.2 m g/h) attenuated the FBF response to MCh significantly (from 28.9 +/- 5 .7 to 21.5 +/- 3.2 ml/min/100 ml tissue at 4 mu g/min; p < 0.05), wher eas both baseline FBF and the response to SNP were unchanged. In concl usion, this investigation showed that commonly used antihypertensive d rugs affect endothelial vasodilator function in a different ways. ACE inhibition enhanced EDV, whereas a nonselective P-blocker attenuated E DV. The calcium channel blocker, verapamil, improved both EDV and EIDV , probably by a direct effect on the vascu lar smooth-muscle cells.