Cyclosporine-induced hypertension in sheep. The role of thromboxanes.

Thromboxanes have been implicated in the CsA-induced hemodynamic changes and impairment in renal function in humans and in rats. We have previously shown that administration of intravenous CsA to sheep for 5 days at 12 mg/kg/day produces a hypertension that is resistance mediated and independent of nephrotoxicity. In this study we used a thromboxane synthetase inhibitor, U63,557A, to examine the role of thromboxanes in the CsA-induced hypertension in the sheep. The thromboxane synthetase inhibitor had no effect on blood pressure in normotensive sheep. Serum thromboxane levels were not elevated with CsA, and the inhibitor had a minimal effect on blood pressure during CsA treatment, suggesting that thromboxanes are not a major contributor to the rise in blood pressure seen in the sheep. A study of the dose-response relationship for CsA at 3, 6, and 24 mg/kg/day for 5 days indicated that maximal blood pressure responses were attained with 6 mg/kg/day.