Divergent effects of different antihypertensive drugs on endothelium-dependent vasodilataiton in the human forearm

• Several studies indicated an abnormal endothelium-dependent vasodilation (EDV) in hypertensive patients, but no study has systematically investigated the effects of different pharmacologic classes of antihypertensive drugs on EDV. This study aimed to evaluate the effects of three different antihypertensive regimens [angiotensin-converting enzyme (ACE) inhibition, calcium channel blockade, and beta-blockade] on EDV when given locally in the forearm at a constant blood pressure. The increase in forearm blood flow (FBF) during local intraarterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation, EIDV) was measured in young, normotensive subjects by venous occlusion plethysmography, before and during concomitant local intraarterial infusion of any of the antihypertensive drugs. Without changing baseline FBF, 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 ml tissue at 4 microg/min; p < 0.05], but the response to SNP was unchanged. Local intraarterial verapamil 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 significantly in parallel (p < 0.05). The local propranolol infusion (n=6, 1.2 mg/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 microg/min; p < 0.05), whereas both baseline FBF and the response to SNP were unchanged. In conclusion, this investigation showed that commonly used antihypertensive drugs affect endothelial vasodilator function in a different ways. ACE inhibition enhanced EDV, whereas a nonselective beta-blocker attenuated EDV. The calcium channel blocker, verapamil, improved both EDV and EIDV, probably by a direct effect on the vascular smooth-muscle cells.

Nyckelord

Antihypertensive drugs

Endothelium

Vasodilation

Methacholine

Nitroprusside

Verapamil

Propranolol

Enalapril

MEDICINE

MEDICIN

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