VASCULAR ENDOTHELIN RESPONSIVENESS AND RECEPTOR CHARACTERISTICS IN-VITRO AND EFFECTS OF ENDOTHELIN RECEPTOR BLOCKADE IN-VIVO IN CYCLOSPORINE HYPERTENSION

1. The aim of these studies was to determine the role of endothelin in cyclosporin A ([CsA], 10 mg/kg per day, s.c., for 30 days) hypertensi on in the rat. 2. There were no significant differences in plasma endo thelin concentrations, in vitro mesenteric vascular membrane [I-125]-e ndothelin-1 (ET-1) binding characteristics or myographic vascular resp onses to endothelin-l between the CsA and control groups (systolic blo od pressure 135+/-1 vs 127+/-1 mmHg, respectively, P<0.001). 3. Twenty -four hours after selective endothelin type A receptor blockade in viv o with BQ123, blood pressure in CsA hypertensive rats was lowered to l evels of normotensive controls. 4. These results suggest that changes in endothelin synthesis rather than changes in vascular sensitivity an d/or ET-1 receptor characteristics may contribute to CsA-induced hyper tension.