Endothelial and vascular smooth muscle function after chronic treatment with cyclosporin A.
We wished to characterize the altered reactivity of vascular smooth muscle and endothelial cells in rat aorta during chronic treatment with cyclosporin. Male adult rats were treated orally for 6 weeks with either cyclosporin A (30 mg/kg/day in 1 ml olive oil, n = 9) or with vehicle alone (n = 10). Rings of isolated thoracic aorta were mounted in organ chambers to measure the change in isometric force in response to smooth muscle-contracting drugs and endothelium-dependent and independent vasodilators. Contractions to potassium chloride (20-80 mM) were markedly reduced in cyclosporin-treated rats. Contractions to phenylephrine (10(-10)-10(-6) M) were reduced at high concentrations (> or = 10(-7) M); those to endothelin-1 (10(-10)-10(-7) M) were not significantly altered. In contrast, contractions to angiotensin II (AII 10(-9)-10(-6) M) were significantly augmented. Endothelium-dependent relaxations to acetylcholine (ACh 10(-8)-10(-5) M) or ADP (10(-7)-10(-5) M) were reduced in cyclosporin-treated rats; endothelium-independent relaxations to SIN-1 (10(-7)-10(-5) M) and atrial natriuretic peptide (ANP 10(-10)-10(-7) M) remained unaffected. Thus, chronic treatment with cyclosporin affects both endothelium-dependent vasodilation and vascular smooth muscle contraction in rat aorta depending on the stimulus applied. The enhanced response to AII and the reduced release of endothelium-derived relaxing factor (EDRF) may contribute to augmented vascular tone and further damage to the arterial wall.
Auch-Schwelk
W
W
Department of Internal Medicine and Cardiology, German Heart Institute Berlin.
Bossaller
C
C
Götze
S
S
Thelen
J
J
Fleck
E
E
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D016572:Cyclosporine / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
D016572:Cyclosporine