Involvement of tyrosine hydroxylase upregulation in cyclosporine-induced hypertension

Japanese Journal of Pharmacology
H ShimizuS Kobayashi

Abstract

To identify the mechanism of cyclosporine-induced hypertension, we studied the effect of cyclosporine on the catecholamine synthetic pathway in rats. We administered cyclosporine (10 mg/kg per day, s.c.) for 3 days to 10-week-old male Wistar rats. Systolic blood pressure increased significantly in the cyclosporine-treated group in comparison to that in the control group. Norepinephrine and epinephrine levels in the adrenal medulla and plasma of cyclosporine-treated rats were also significantly higher than levels in the control rats. Moreover, tyrosine hydroxylase (TH) activity and TH mRNA expression in the adrenal medulla of cyclosporine-treated rats were significantly elevated. Administration of the TH inhibitor alphamethyl-p-tyrosine (200 mg/kg, b.i.d., s.c.) for 3 days significantly suppressed cyclosporine-induced increases in systolic blood pressure. Phosphorylation of cyclic AMP responsive element-binding protein (CREB) and its binding activity to DNA in the nuclear fraction from the adrenal medulla of cyclosporine-treated rats were much higher than that of the control rats. Calcineurin protein expression of cyclosporine-treated rats was less than that of the control rats. These results suggest that cyclosporine increased ...Continue Reading

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Citations

Aug 2, 2003·Clinical and Experimental Pharmacology & Physiology·Toshio KumaiShinichi Kobayashi
Sep 17, 2004·Biochemical and Biophysical Research Communications·Laura EzquerraThomas F Deuel
Jul 14, 2016·The Journal of Pharmacology and Experimental Therapeutics·Alexandra E Soto-PiñaRandy Strong
Mar 25, 2021·Acta Diabetologica·Giovanna CastoldiCira R T di Gioia

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