Functional angiotensin and endothelin, but not thromboxane, pathways are necessary for the hypertension and baroreflex dysfunction caused by cyclosporine in rats (LB565)

We investigated the effects of pharmacologic interventions that selectively interrupt angiotensin II (Ang II), endothelin (ET), or ‎thromboxane (TXA2) signaling on CSA-evoked hypertension and arterial baroreflex impairment in conscious rats. Baroreflex ‎curves relating changes in heart rate (HR) to increases (phenylephrine, PE) or decreases (sodium nitroprusside, SNP) in blood ‎pressure (BP) were constructed and slopes of the curves were taken as a measure of baroreflex sensitivity (BRSPE and BRSSNP). ‎CSA (25 mg/kg/day i.p., 7 days) significantly increased BP and HR and attenuated reflex HR responses and slopes of the ‎baroreflex curves generated by PE and SNP. Concurrent blockade of ETA (atrasentan) or AT1 receptors (losartan), or inhibition of ‎angiotensin converting enzyme (captopril) reduced the hypertensive, but not the tachycardic, effect of CSA. Further, atrasentan ‎reversed the CSA-evoked impairment in both BRSPE and BRSSNP whereas losartan or captopril selectively improved BRSPE. The ‎blockade o...