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 chronic central infusion of sodium, increased brain "ouabain" results in sympathetic hyperactivity and hypertension, possibly by activating the brain renin-angiotensin system. In the present study, we tested whether the hypertension caused by exogenous ouabain also depends on activation of brain renin-angiotensin system. In Wistar rats, ouabain (50 [micro sign]g/d) was infused subcutaneously 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 pressure, heart rate, central venous pressure, and renal sympathetic nerve activity were recorded in conscious rats at rest and in response to air-jet stress, intracerebroventricular injection of the alpha2-agonist guanabenz (25 and 75 [micro sign]g) or angiotensin II (30 ng), acute volume expansion, and ramp changes of blood pressure by +/- 50 mm Hg with phenylephrine and nitroprusside. Compared with control rats, in rats treated with ouabain, resting mean arterial pressure was significantly increased (111 +/- 4 versus 93 +/- 3 mm Hg; P