Endothelial Dysfunction and Subendothelial Monocyte Macrophages in Hypertension: Effect of Angiotensin Converting Enzyme Inhibition

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 18; no. 2; pp. 132 - 141
• Main Authors: Clozel, Martine, Kuhn, Herbert, Hefti, Fridolin, Baumgartner, Hans R
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.08.1991; Hagerstown, MD Lippincott
• Subjects: Acetylcholine - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Antihypertensive agents; Aorta - drug effects; Aorta - pathology; Biological and medical sciences; Captopril - pharmacology; Cardiovascular system; Carotid Arteries - drug effects; Carotid Arteries - pathology; Cell Movement - drug effects; Cilazapril; Dose-Response Relationship, Drug; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Hypertension - drug therapy; Hypertension - physiopathology; Macrophages - physiology; Male; Medical sciences; Norepinephrine - pharmacology; Peptidyl-Dipeptidase A - physiology; Pharmacology. Drug treatments; Pyridazines - pharmacology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renal Artery - drug effects; Renal Artery - pathology; Serotonin - pharmacology; Vasoconstriction - drug effects; Vasodilation - drug effects; Hypertension; Rat; Enzyme; Rodentia; Enzyme inhibitor; Cardiovascular disease; Artery; Endothelium; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Angiotensin converting enzyme; Antihypertensive agent; Infiltration; Hemodynamics; Macrophage
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.18.2.132

Hypertension is associated with an impairment of endothelium-dependent relaxation. The angiotensin converting enzyme inhibitors captopril and cilazapril can prevent this endothelial dysfunction. We recently observed that long-term treatment with cilazapril could also prevent subendothelial infiltration by mononuclear cells in spontaneously hypertensive rats. This prompted us to examine whether, in spontaneously hypertensive rats, endothelial dysfunction and subendothelial infiltration by mononuclear cells are associated. These cells were characterized as monocyte macrophages. Infiltration by monocyte macrophages was quantified by morphometry. Endothelial function was estimated by calculating serotonin ratio (maximal contraction to serotonin on isolated arterial rings with endothelium over maximal contraction on paired rings without endothelium). The regional distribution of endothelial dysfunction and subendothelial monocyte macrophages was similar. Both were maximal in the carotid artery, less in the aorta, and nonexistent in the renal artery. A 2-week treatment with cilazapril decreased both endothelial dysfunction (serotonin ratio decreased by 32%) and the number of subendothelial monocyte macrophages in the aorta, which decreased by 38%. We conclude that in spontaneously hypertensive rats, endothelial dysfunction and subendothelial monocyte macrophage infiltration are associated and that cilazapril can decrease both. The observation that angiotensin converting enzyme inhibitors affect subendothelial accumulation of monocyte macrophages may lead to a better understanding of the mechanism of action of this class of drugs.