Both brain angiotensin II and "ouabain" contribute to sympathoexcitation and hypertension in Dahl S rats on high salt intake

Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats from 5 to 9 w eeks of age received a regular or high salt diet and concomitantly an intra cerebroventricular infusion of the angiotensin type 1 blocker losartan (1 m g . kg(-1) . d(-1)) or antibody Fab fragments, which bind ouabain and relat ed steroids with high affinity, or gamma-globulins as control (200 mu g/d f or both). At 9 weeks of age, blood pressure (BP), heart rate (HR), central venous pressure, and renal sympathetic nerve activity were recorded in cons cious rats at rest and in response to air stress and to intracerebroventric ular alpha(2)-agonist guanabenz (50 mu g) and ouabain (0.5 mu g). Barorefle x function was assessed by acute volume expansion with intravenous 5% dextr ose and ramp changes of BP by +/-50 mm Hg induced by intravenous phenylephr ine and sodium nitroprusside. In Dahl S but not R rats, high salt significa ntly increased BP and HR; enhanced BP, HR, and renal sympathetic nerve acti vity responses to air stress and guanabenz; and attenuated cardiopulmonary and arterial baroreflex control of renal sympathetic nerve activity and HR. Both losartan and Fab fragments prevented these responses to high salt to a similar extent in Dahl S rats but had no effect in Dahl R rats on high sa lt. Sympathoexcitatory responses to ouabain were attenuated in Dahl S on hi gh versus regular salt and were abolished in Dahl R or S treated with losar tan or Fab fragments. Consistent with previous studies in SHR, the present data indicate that in Dahl S on high salt, both brain "ouabain" and angiote nsin II contribute to decreased sympathoinhibition and increased sympathoex citation, impairment of baroreflex, and therefore hypertension.