EFFECTS OF CILAZAPRIL ON VASCULAR STRUCTURE AND FUNCTION IN ESSENTIAL-HYPERTENSION

Hypertension is associated with an altered design of resistance vessel s and decreased endothelium-dependent vasodilator response to acetylch oline. A role of angiotensin II in both defects is suggested by animal experiments in which angiotensin-converting enzyme inhibition reverte d structural and functional changes. We investigated the effects of 20 weeks of therapy with the angiotensin-converting enzyme inhibitor cil azapril (5 mg twice daily) on the endothelium-dependent response to br achial artery infusions of acetylcholine and the endothelium-independe nt vascular relaxation after sodium nitroprusside in 22 subjects with mild to moderate essential hypertension. In addition, we measured mini mal forearm vascular resistance (ratio of mean arterial pressure and f orearm blood flow after heating, ischemia, and ischemic exercise) as a n indirect estimate of vascular structure. Cilazapril decreased blood pressure (151+/-14/99+/-7 mm Hg during placebo to 138+/-17/89+/-8 mm H g after cilazapril treatment, P<.01) and baseline (42.2+/-12.6 to 37.1 +/-10.6 U, P<.05) and minimal (3.0+/-1.1 to 2.4+/-0.7 U, 15.9+/-20.2%; P<.05) forearm vascular resistances. The change in minimal forearm va scular resistance was unrelated to age, duration of hypertension, or c hanges in blood pressure. Sodium nitroprusside increased forearm blood flow from 2.6+/-1.0 to 11.4+/-5.9 mL/min per 100 mL and acetylcholine to 21.5+/-17.8. Both responses did not change after cilazapril. The d ata provide indirect evidence that cilazapril therapy may improve vasc ular structure in human hypertension. The lack of relationship between vascular and blood pressure changes would be compatible with experime ntal evidence supporting a role for angiotensin II in the development and regression of vascular changes, but this needs further study. Ther apy with cilazapril for 20 weeks, like other antihypertensive therapy, does not seem to influence endothelial vasodilator function in humans to a significant degree.