title: Mechanisms mediating sodium-induced pressor responses in the PVN of Dahl rats.
abstract: Intracerebroventricular infusion of Na(+)-rich artificial cerebrospinal fluid (aCSF) causes larger sympathetic and pressor responses in Dahl salt-sensitive (S) than -resistant (R) or Wistar rats. Enhanced activity of the aldosterone-"ouabain" pathway or decreased nitric oxide (NO) release may contribute to this enhanced responsiveness. Where in the brain these mechanisms interact is largely unknown. The present study evaluated whether Na(+) in the paraventricular nucleus (PVN) causes larger pressor responses in Dahl S (SS/Mcw) than R (Dahl SS.BN13) rats and whether mineralocorticoid receptors, benzamil-blockable Na(+) channels, "ouabain," angiotensin type 1 receptors, or NO mediates these enhanced responses. Na(+)-rich aCSF in the PVN caused 30-40% larger increases in blood pressure and heart rate in Dahl S than R or Wistar rats, whereas responses to ouabain, ANG II, or N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME) in the PVN were the same. These responses to Na(+) were not affected by eplerenone, benzamil, or Fab fragments, whereas they were fully blocked by losartan, in Dahl S and R rats. l-NAME enhanced them more in Dahl R than S rats, thereby equalizing the responses in the two strains. Pressor responses to l-NAME in the PVN were attenuated by a high-salt diet in Dahl S, but not R, rats. The results indicate that acute and chronic increases in Na(+) concentration in the PVN inhibit NO release in the PVN of Dahl S, but not R, rats, thereby contributing to the enhanced pressor responses to Na(+) in Dahl S rats.
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gabor
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006339:Heart Rate; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D057967:Infusions, Intraventricular; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D020303:Rats, Inbred Dahl; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D015398:Signal Transduction; D012964:Sodium / Q000008:administration & dosage / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000008:administration & dosage; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D017673:Sodium Chloride, Dietary; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004791:Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D018161:Receptors, Mineralocorticoid; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D009569:Nitric Oxide; D012964:Sodium; D019001:Nitric Oxide Synthase