title: Brain "ouabain" mediates the sympathoexcitatory and hypertensive effects of high sodium intake in Dahl salt-sensitive rats.
abstract: To assess whether brain ouabain-like activity (OLA) mediates the hypertensive effects of high sodium intake in Dahl salt-sensitive (Dahl S) rats, the effects of blockade of brain OLA on mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were evaluated in conscious Dahl salt-resistant (Dahl R) and Dahl S rats on a regular (120 mumol/g) or high sodium (1370 mumol/g) diet from 4 to 7 weeks of age. Dahl S rats given high sodium showed higher basal MAP and augmented responses of MAP and RSNA to air stress and to intracerebroventricular injection of the alpha 2-adrenergic receptor agonist guanabenz as compared with Dahl R rats or Dahl S rats given regular sodium. In contrast, the sympathoexcitatory and pressor responses to intracerebroventricular injection of ouabain (0.3 and 1.0 microgram) were markedly attenuated in Dahl S rats given high sodium. Intracerebroventricular preinjection of 0.3 microgram ouabain significantly enhanced blood pressure and RSNA responses to air stress and intracerebroventricular guanabenz in Dahl S rats given regular sodium to the levels observed in Dahl S rats given high sodium. Intracerebroventricular digoxin-specific antibody Fab (DAF) fragments (132 micrograms/8 microL for 5 minutes) did not change basal MAP and RSNA during the first 4 hours after administration in Dahl S rats on a high sodium diet for 3 weeks. However, 18 hours after the injection of DAF fragments, basal MAP and RSNA were significantly decreased, reaching values for Dahl S rats on a regular sodium diet. The magnitude of increases or decreases in MAP and RSNA to air stress or intracerebroventricular guanabenz were significantly attenuated by the DAF fragments in Dahl S rats on a high sodium but not regular sodium diet. Concomitant intracerebroventricular infusion of DAF fragments (200 micrograms per day) prevented the development of hypertension after a high sodium diet in Dahl S rats and prevented an augmentation in pressor and sympathoexcitatory responses to air stress. After discontinuing the infusion of DAF fragments, resting MAP gradually increased to the high levels found in Dahl S rats given high sodium treated with gamma-globulins. These results support the concept that high sodium intake may cause hypertension in Dahl S rats by increasing endogenous brain OLA, thereby enhancing sympathetic outflow and basal blood pressure as well as sympathoexcitatory and pressor responses to stress.
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
authors.forename: B S
authors.initials: BS
authors.lastname: Huang
authors.forename: F H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000209:etiology* / Q000517:prevention & control; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007668:Kidney / Q000294:innervation*; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D012982:Sodium, Dietary / Q000008:administration & dosage*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D007140:Immunoglobulin Fab Fragments; D012982:Sodium, Dietary; C050199:digoxin antibodies Fab fragments; D010042:Ouabain