Antihypertensive treatment and endothelial vasodilatory function

Sammanfattning: The endothelium integrates vascular tone by the synthesis of vasoactive substances secreted abluminally to the underlying vascular smooth muscle. Endothelial function has previously been shown to be impaired in primary, secondary and experimental forms of hypertension. In this thesis the influence of antihypertensive drugs on endothelium-dependent vasodilation (EDV) was evaluated in the in vivo circulation of the human forearm. Ambulatory blood pressure (ABP) was not found to be more closely related to endothelial vasodilatory function than office blood pressure. Within the hypertensive group, there was a relationship between the white-coat effect and EDV. Local infusion of principally different beta-blocking agents induced divergent effects on EDV. In normotensive subjects propranolol impaired EDV, atenolol showed a tendency to improve EDV and labetalol enhanced both EDV and endothelium-independent vasodilation (EIDV). Drugs commonly used in the treatment of hypertension and congestive heart failure were also evaluated by local infusions in normotensive subjects. Without lowering blood pressure, enalaprilat and furosemide improved EDV, whereas no major effects were induced by digoxin or metoprolol. Furthermore, locally given captopril and systemically administered enalaprilat acutely improved EDV in patients with untreated hypertension and in normotensive subjects. After 3 months of randomized, double-blind treatment with the angiotensin II subtype-1(AT1) receptor antagonist irbesartan, or the β1-selective adrenoreceptor antagonist atenolol improved EDV. In conclusion, antihypertensive drugs were found to have a divergent influence on endothelial vasodilatory function in acute studies, whereas antihypertensive treatment for 3 months improved EDV in a randomized double-blind trial.