Ventrolateral medulla AT1 receptors support arterial pressure in Dahl salt-sensitive rats.
The present study addresses the hypothesis that angiotensin type 1 receptors (AT1Rs) in the rostral ventrolateral medulla (RVLM) contribute to the elevation of mean arterial pressure (MAP) in Dahl salt-sensitive (DS) rats fed a diet with a high NaCl content. Groups of DS or Dahl salt-resistant (DR) rats were fed diets containing either 0.3% NaCl (LNa) or 8% NaCl (HNa) for 3 weeks. Rats were anesthetized with alpha-chloralose, and the effects of microinjecting the AT1R antagonist valsartan (Val) or angiotensin II (Ang II) into the RVLM on MAP were measured. Bilateral injection of 100 pmol Val into the RVLM reduced the elevated MAP in the DS-HNa rats by approximately 35 mm Hg. In contrast, Val had no effect on MAP in DS-LNa rats. DR rats were normotensive on either diet; Val injection into the RVLM had no significant effect on MAP in DR-HNa rats but did evoke a small decrease in MAP in DR-LNa rats. Injection of Ang II into the RVLM increased arterial pressure in all groups, but the response was substantially larger in DS-HNa rats. Inhibition of neuronal function in the vicinity of the hypothalamic paraventricular nucleus, a possible source of innervation of the RVLM AT1R, by local injection with muscimol also produced a substantial decrease in MAP in DS-HNa rats but not in DS-LNa rats or DR rats. Thus, RVLM AT1Rs appear to contribute to salt-dependent hypertension in DS rats, and the paraventricular nucleus may be a source of this tonic activation.
Ito
Satoru
S
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hiratsuka
Makoto
M
Komatsu
Kazutoshi
K
Tsukamoto
Kazuyoshi
K
Kanmatsuse
Katsuo
K
Sved
Alan F
AF
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000503:physiopathology*; D010286:Paraventricular Hypothalamic Nucleus / Q000503:physiopathology; D051381:Rats; D020303:Rats, Inbred Dahl; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology*; D012965:Sodium Chloride / Q000008:administration & dosage; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D012965:Sodium Chloride; D000068756:Valsartan; D014633:Valine