enalapril and Vasculitis

Angiotensin converting enzyme (ACE) inhibitors prevent a wide variety of key events underlying atherogenesis. Whether these actions depend solely on reduction of angiotensin II (Ang II) generation is still to be determined. This study was undertaken to determine whether enalapril, an ACE inhibitor, prevents atherosclerosis and vascular inflammation induced by Ang II in apolipoprotein E-deficient (apoE-KO) mice. Subcutaneous infusion of Ang II (1.44 mg/(kg day)) for 4 weeks increased blood pressure and accelerated atherosclerosis development in the carotid arteries. The expression of the endothelial adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as well as the chemokines monocyte chemotactic protein-1 (MCP-1) and macrophage-colony stimulating factor (M-CSF) was up-regulated in the aortas of Ang II-treated mice. Enalapril co-treatment (25 mg/(kg day), in drinking water) prevented the development of atherosclerosis without affecting blood pressure or circulating cholesterol. In addition to preventing the Ang II-induced over-expression of adhesion molecules and chemokines in the aorta, enalapril up-regulated the expression of peroxisome proliferator-activated receptors (PPARs)-alpha and -gamma, potential anti-inflammatory transcription factors. In the aortic arch, a lesion-prone site, the co-treatment with enalapril reduced the percentage of arterial wall occupied by macrophages and foam cells, medial sclerosis and elastin reduplication. Together, these data suggest an important role for Ang II-independent mechanisms in the antiatherogenic and anti-inflammatory effects of ACE inhibitors.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Aortic Aneurysm; Apolipoproteins E; Arteriosclerosis; Cell Adhesion Molecules; Chemokines; Enalapril; Endothelium; Gene Expression; Male; Mice; Mice, Knockout; PPAR alpha; PPAR gamma; RNA, Messenger; Up-Regulation; Vasculitis

We report a case of vasculitis in a 67-year-old woman who successively developed over a four-month period clinical manifestations suggestive of rheumatoid arthritis, lupus, sicca, syndrome and finally giant cell arteritis. All her symptoms resolved promptly upon discontinuation of enalapril and none recurred over the five-year follow-up period. The only residual manifestation is Jaccoud's arthropathy of the hands.

Topics: Aged; Antihypertensive Agents; Arthritis, Rheumatoid; Diagnosis, Differential; Enalapril; Female; Follow-Up Studies; Giant Cell Arteritis; Hand; Humans; Lupus Vulgaris; Sjogren's Syndrome; Vasculitis

Our pharmacologic armamentarium is expanding at a tremendous pace, and requires that we as clinicians maintain a certain level of knowledge of the drugs that we use, as well as their metabolism, and how they may function, both positively and negatively, in a given patient. Certain drugs, such as the angiotensin-converting enzyme inhibitors, interfere with the natural deactivation of certain vasoactive substances normally present in the body. Since many of these systems are functionally interrelated (eg, angiotensin-converting enzyme and kininase II), we may see cutaneous side effects when these drugs are administered. Enalapril is an angiotensin-converting enzyme inhibitor that promoted a cutaneous eruption in a patient with renal failure secondary to diabetes. We suspect that our patient's vasculitis and maculopapular erythema is included in a large number of polymorphic eruptions that can be seen with angiotensin-converting enzyme inhibitors, and review the operative pathogenetic mechanism. Many of these side effects are dose related, and can be controlled or eliminated by lowering the dosage of angiotensin-converting enzyme inhibitor, depending upon the clinical circumstances.

Topics: Adult; Drug Eruptions; Enalapril; Erythema; Female; Humans; Skin; Vasculitis

Topics: Drug Eruptions; Enalapril; Female; Humans; Middle Aged; Vasculitis

Topics: Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Lisinopril; Male; Middle Aged; Vasculitis