Effects of angiotensin converting enzyme inhibition on endothelial vasodilator function in primary human hypertension.
Hypertension in animal models and in humans is associated with a decreased vasodilator response to acetylcholine which causes vascular relaxation by release of endothelium-derived relaxing factor from the endothelium. Since lowering of blood pressure, particularly with angiotensin converting enzyme inhibitors, improved the response to acetylcholine we investigated the effects of brachial artery infusions of ascending dosages of acetylcholine on forearm blood flow before and after 5 months of therapy with the angiotensin converting enzyme inhibitor, cilazapril, in 10 patients with mild to moderate primary hypertension. Cilazapril decreased blood pressure from 150.8 +/- 14.4/98.9 +/- 4.3 mmHg during placebo to 138.8 +/- 15.6/88.6 +/- 8.9 mmHg (P < 0.01). Brachial artery acetylcholine infusions increased forearm blood flow from 2.95 +/- 1.5 to a maximum of 22.8 +/- 11.5 ml.min-1.100 ml-1 forearm tissue and decreased forearm vascular resistance from 48.1 +/- 34.1 to 6.9 +/- 6.9 units before cilazapril. This response did not change after cilazapril therapy. Our findings in patients with primary hypertension, therefore, do not support the concept that angiotensin converting enzyme inhibition influences endothelium-dependent vascular relaxation to acetylcholine to a significant degree. Whether this lack of effect on endothelial vasodilator function is specific for the vascular bed chosen for study or whether it represents a fundamental difference between animal models and human hypertension remains an important issue to be clarified.
Kiowski
W
W
Department of Internal Medicine, University Hospital, Zurich, Switzerland.
Linder
L
L
Nuesch
R
R
Martina
B
B
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D017315:Cilazapril / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D016037:Single-Blind Method; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D017315:Cilazapril; D000109:Acetylcholine