title: Cardiovascular effects of angiotensin II and glutamate in the PVN of Dahl salt-sensitive rats.
abstract: Several models of chronic sympathetic hyperactivity are associated with an increase in excitatory angiotensinergic and glutamatergic activity, and a decrease in GABAergic activity in the PVN. The present study evaluated whether activation of glutamate and AT1 receptors in the PVN contributes to the maintenance of resting BP in Dahl salt sensitive (S) rats on regular or high salt diet for 4-6 weeks. Candesartan and kynurenate were infused bilaterally into the PVN and BP and heart rate (HR) were recorded. Both candesartan and kynurenate in the PVN did not change MAP and HR in normotensive Dahl salt resistant (R) and S rats on regular salt diet or in R rats on high salt diet. In hypertensive Dahl S rats on high salt diet, candesartan decreased MAP (-14±2 mm Hg), and tended to increase HR (22±5 bpm). Kynurenate decreased both MAP (-22±3 mm Hg) and HR (-42±7 bpm) in these rats. At the peak BP decrease by candesartan, kynurenate in the PVN further decreased BP by ~50% (-14±2 mm Hg), whereas candesartan did not further decrease BP at the peak BP response to kynurenate (-4±2 mm Hg). These results indicate that activation of glutamate and AT1-receptors in the PVN contributes to the maintenance of BP in hypertensive Dahl S rats, but not normotensive Dahl S and R rats. The increased BP response to AT1-receptor activation in the PVN of hypertensive Dahl S appears to be mediated by enhanced local glutamate receptor activation, but another mechanism(s) appears to further enhance glutamate responses.
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 / Q000502:physiology*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007736:Kynurenic Acid / Q000008:administration & dosage; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020303:Rats, Inbred Dahl; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000008:administration & dosage
chemical_list: C524087:Agtrap protein, rat; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D018698:Glutamic Acid; D007736:Kynurenic Acid; C081643:candesartan