Prolonged NOS inhibition in the brain elevates blood pressure in normotensive rats.
Systemic inhibition of nitric oxide synthase (NOS) evokes hypertension, which is enhanced by salt loading, partly via augmented sympathetic activity. We investigated whether inhibition of brain NOS elevates blood pressure (BP) in normotensive rats and, if so, whether the BP elevation is enhanced by salt loading. After a 2-wk low-salt (0.3%) diet, male Sprague-Dawley (SD) rats were divided into four groups. Groups 1 and 2 received a chronic intracerebroventricular infusion of 0.5 mg . kg-1 . day-1 of NG-monomethyl-L-arginine (L-NMMA), and groups 3 and 4 were given artificial cerebrospinal fluid (aCSF). Groups 1 and 3 were placed on a high-salt (8%) diet, whereas groups 2 and 4 were on a low-salt diet. On day 9 or 10, group 1 showed significantly higher mean arterial pressure (MAP) in a conscious unrestrained state (129 +/- 3 mmHg vs. 114 +/- 3, 113 +/- 1, and 108 +/- 3 mmHg in groups 2, 3, and 4, respectively, P < 0.05). On a high-salt diet, response of renal sympathetic nerve activity but not of BP to air-jet stress was significantly larger in rats given L-NMMA than in rats given aCSF (29 +/- 4% vs. 19 +/- 3%, P < 0.05). When the intracerebroventricular infusions were continued for 3 wk, MAP was significantly higher in rats given L-NMMA than in rats given aCSF irrespective of salt intake, although the difference was approximately 7 mmHg. Thus chronic inhibition of NOS in the brain only slightly elevates BP in SD rats. Salt loading causes a more rapid rise in BP. The mechanisms of the BP elevation and its acceleration by salt loading remain to be elucidated.
Third Department of Internal Medicine, University of the Ryukyus School of Medicine, 207 Uehara, Nishihara-cho, Okinawa 903-01, Japan.
A
A
Sakima
H
H
Teruya
M
M
Yamazato
R
R
Matayoshi
H
H
Muratani
K
K
Fukiyama
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004039:Diet, Sodium-Restricted; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D007263:Infusions, Parenteral; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D012982:Sodium, Dietary / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology*
D012982:Sodium, Dietary; D019323:omega-N-Methylarginine; D012964:Sodium; D019001:Nitric Oxide Synthase