Altered pressor responses to NE and ANG II during cyclosporin A administration to conscious rats

Vasoconstriction and hypertension have been prominent during cyclosporin A (CSA) administration. To evaluate whether CSA modulates vascular responsiveness to pressor stimuli in the intact organism, CSA was administered via osmotic pump (10 and 20 mg.kg-1.day-1 ip vs. olive oil vehicle) for 2 wk. After 8 days, arterial pressure and dose-response relationships to norepinephrine, angiotensin II, and bradykinin were measured in conscious animals. Despite similar initial pressures, dose-response relationships were markedly attenuated to both norepinephrine and angiotensin II. Maximal responses were not affected, indicating a rightward shift without loss of peak effect. Vasodilation with bradykinin was not diminished. These changes were not evident after an acute CSA infusion at the same dose (10 mg.kg-1.day-1 over 2 h). Treatment with verapamil (0.505 mg/kg over 2 days) lowered basal arterial pressures but did not change the effects of CSA on pressor sensitivity. Despite attenuated pressor responses, renal vascular resistance was elevated and glomerular filtration diminished during CSA administration. These observations indicate that cyclosporin modifies vascular responsiveness to pressor stimuli in the rat and may explain the relative resistance of this species to cyclosporin-induced hypertension.