Effect of antihypertensive treatment on endothelium-dependent vascular relaxation in patients with essential hypertension

Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.

OBJECTIVES. This study was designed to determine whether antihypertensive treatment can restore the impaired endothelium-dependent vasodilation of patients with essential hypertension. BACKGROUND. The endothelium regulates vascular tone through the release of vasoactive agents that act on the underlying vascular smooth muscle. This endothelial function is impaired in certain cardiovascular conditions, including essential hypertension. METHODS. The vascular responses to acetylcholine (endothelium-dependent vasodilator, 7.5, 15 and 30 micrograms/min) and sodium nitroprusside (direct dilator of smooth muscle, 0.8, 1.6, 3.2 micrograms/min) were studied in 15 patients (11 men and 4 women with a mean age of 54.1 +/- 12 years) on two occasions: after withdrawal of medications, when the patients were hypertensive, and during the medical treatment that reduced blood pressure to within normal limits in each patient. The results were compared with those obtained in 15 normal control subjects (10 men and 5 women with a mean age of 52.3 +/- 7 years). Drugs were infused into the brachial artery, and forearm blood flow response was measured by strain gauge plethysmography. RESULTS. The blood flow and vascular resistance responses to acetylcholine were significantly reduced in the hypertensive patients (p < 0.0001); maximal forearm flow (ml/min per 100 ml) was 7.0 +/- 4 ml in the patients and 16.7 +/- 5 in the control subjects (p < 0.005). However, no significant differences between groups were observed in the responses to sodium nitroprusside. In patients with essential hypertension, the vascular responses to acetylcholine and sodium nitroprusside were not modified by medical therapy. Maximal forearm flow with acetylcholine (ml/min per 100 ml) was 7.2 +/- 2 during antihypertensive therapy and 7.0 +/- 4 after medication withdrawal. CONCLUSIONS. Clinically effective antihypertensive therapy does not restore the impaired endothelium-dependent vascular relaxation of patients with essential hypertension. This indicates that such endothelial dysfunction is either primary or becomes irreversible once the hypertensive process has become established.

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