title: Central infusion of aliskiren prevents sympathetic hyperactivity and hypertension in Dahl salt-sensitive rats on high salt intake.
abstract: Central infusion of an angiotensin type 1 (AT(1)) receptor blocker prevents sympathetic hyperactivity and hypertension in Dahl salt-sensitive (S) rats on high salt. In the present study, we examined whether central infusion of a direct renin inhibitor exerts similar effects. Intracerebroventricular infusion of aliskiren at the rate of 0.05 mg/day markedly inhibited the increase in ANG II levels in the cerebrospinal fluid and in blood pressure (BP) caused by intracerebroventricular infusion of rat renin. In Dahl S rats on high salt, intracerebroventricular infusion of aliskiren at 0.05 and 0.25 mg/day for 2 wk similarly decreased resting BP in Dahl S rats on high salt. In other groups of Dahl S rats, high salt intake for 2 wk increased resting BP by ∼25 mmHg, enhanced pressor and sympathoexcitatory responses to air-stress, and desensitized arterial baroreflex function. All of these effects were largely prevented by intracerebroventricular infusion of aliskiren at 0.05 mg/day. Aliskiren had no effects in rats on regular salt. Neither high salt nor aliskiren affected hypothalamic ANG II content. These results indicate that intracerebroventricular infusions of aliskiren and an AT(1) receptor blocker are similarly effective in preventing salt-induced sympathetic hyperactivity and hypertension in Dahl S rats, suggesting that renin in the brain plays an essential role in the salt-induced hypertension. The absence of an obvious increase in hypothalamic ANG II by high salt, or decrease in ANG II by aliskiren, suggests that tissue levels do not reflect renin-dependent ANG II production in sympathoexcitatory angiotensinergic neurons.
authors.affiliation: Hypertension Unit, Univ. of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Bing S
authors.initials: BS
authors.lastname: Huang
authors.forename: Roselyn A
authors.initials: RA
authors.lastname: White
authors.forename: Li
authors.initials: L
authors.lastname: Bi
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000577:Amides / Q000008:administration & dosage*; D000804:Angiotensin II / Q000134:cerebrospinal fluid; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005650:Fumarates / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects; D006948:Hyperkinesis / Q000503:physiopathology / Q000517:prevention & control*; D006973:Hypertension / Q000503:physiopathology / Q000517:prevention & control*; D057967:Infusions, Intraventricular; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013564:Sympathetic Nervous System / Q000187:drug effects*; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000804:Angiotensin II; D005650:Fumarates; D017673:Sodium Chloride, Dietary; D000092502:Renin Inhibitors; C446481:aliskiren