Medicaid and immunization coverage.
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Child, Preschool↗
Biomedical subjects
J Thelen
Publications and source records attributed to J Thelen.
Preventive effects of diltiazem on cyclosporin A-induced vascular smooth muscle dysfunction.
Cyclosporin A may cause vascular smooth muscle dysfunction due to calcium overload as a consequence of chronically augmented calcium influx. In the present study, the responsiveness to vasocontrictors was investigated in rats after chronic treatment for 6 weeks with placebo, cyclosporin A (30 mg/kg per day), diltiazem (60 mg/kg per day), or cyclosporin A plus diltiazem. Twenty-four hours after the last oral treatment the animals were sacrificed and rings of the thoracic aorta were suspended in organ chambers under isometric conditions in the absence of cyclosporin A or diltiazem. Chronic treatment with cyclosporin A significantly augmented contractions to angiotensin II (10(-9)-10(-5) M). This effect was prevented by cotreatment with diltiazem. Diltiazem did not affect the cyclosporin A-induced reduction in the response to potassium chloride (10-80 mM). The contractions to phenylephrine (10(-9)-10(-6) M) and endothelin-1 (10(-9)-10(-7) M) were not significantly different in the four groups. The preventive effect of diltiazem against the cyclosporin A-induced hypersensitivity to angiotensin II supports the hypothesis of increased calcium influx during cyclosporin A therapy. The results may provide an additional rationale for the use of calcium antagonists in the treatment of the vascular side effects of cyclosporin A.
Animals↗
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.
Animals↗
Calcium entry blockade may prevent cyclosporin A-induced hypersensitivity to angiotensin II and endothelial dysfunction in the rat aorta.
Vascular smooth muscle dysfunction after chronic treatment with cyclosporin A was in part explained by chronically augmented calcium influx leading to calcium overload. The potential protective effect of calcium antagonism with diltiazem as regards endothelial and vascular smooth muscle reactivity was investigated during chronic treatment with cyclosporin A. Male Wistar rats were orally treated for 6 weeks with either cyclosporin A (30 mg.kg-1 x day-1 in 1 ml, n = 8), with the vehicle alone (n = 10), with diltiazem (60 mg.kg-1 x day-1, n = 10) or with a combination of cyclosporin A and diltiazem (30 mg.kg-1 x day-1 and 60 mg.kg-1 x day-1, n = 8), respectively. Rings of the isolated thoracic aorta were mounted in organ chambers to measure isometric force. Chronic treatment with diltiazem alone did not affect the responsiveness to any of the drugs tested, but the augmentation of contractions to angiotensin II (10(-9) to 10(-6) M) after treatment with cyclosporin, was prevented by co-treatment with diltiazem. Co-treatment with diltiazem, however, did not affect the response to potassium chloride (20-80 mM), endothelin-1 (10(-9) to 10(-7) M) or phenylephrine (10(-9) to 10(-6) M). Endothelium-dependent relaxations to calcitonin gene-related peptide (CGRP, 10(-10) to 10(-7) M) and acetylcholine (10(-8) to 10(-5) M) were reduced in cyclosporin A treated rats. Co-treatment with diltiazem normalized the response to CGRP. The response to acetylcholine was not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗