Brain renin-angiotensin system and ouabain-induced sympathetic hyperactivity and hypertension in Wistar rats

In Dahl salt-sensitive rats on a high salt diet or normotensive rats with c hronic central infusion of sodium, increased brain "ouabain" results in sym pathetic hyperactivity and hypertension, possibly by activating the brain r enin-angiotensin system. In the present study, we tested whether the hypert ension caused by exogenous ouabain also depends on activation of brain reni n-angiotensin system. In Wistar rats, ouabain (50 mu g/d) was infused subcu taneously for 14 days with the use of osmotic minipumps. Concomitantly, in one group, the angiotensin II type 1 receptor blocker losartan (1 mg/kg per day) was infused intracerebroventricularly. On day 15, mean arterial press ure, heart rate, central venous pressure, and renal sympathetic nerve activ ity were recorded in conscious rats at rest and in response to air-jet stre ss, intracerebroventricular injection of the alpha(2)-agonist guanabenz (25 and 75 mu g) or angiotensin II (30 ng), acute volume expansion, and ramp c hanges of blood pressure by +/-50 mmHg with phenylephrine and nitroprusside . Compared with control rats, in rats treated with ouabain, resting mean ar terial pressure was significantly increased (111+/-4 versus 93+/-3 mm Hg; P <0.05), and increases or decreases in mean arterial pressure, heart rate, a nd renal sympathetic nerve activity in response to air stress or guanabenz were enhanced significantly. These effects of ouabain were prevented when l osartan was given concomitantly. Maximal slopes of arterial baroreflex cont rol of renal sympathetic nerve activity and heart rate tended to be decreas ed in ouabain-treated versus control rats and were significantly increased in ouabain-treated rats with versus without losartan. No differences in car diopulmonary baroreflex function were detected. It seems that by day 14 to 15, the central effect of ouabain on baroreflex control prevails over its p eripheral sensitizing effect on baroreceptors, leading to a tendency of des ensitization. These results indicate that chronic administration of ouabain activates the brain renin-angiotensin system, resulting in decreased sympa thoinhibition and increased sympathoexcitation, impairment of baroreflex fu nction, and hypertension.