title: High blood pressure enhances brain stem neuronal nitric oxide synthase activity in Dahl salt-sensitive rats.
abstract: The aims of the present study were to determine the mechanism underlying enhanced neuronal nitric oxide synthase (nNOS) activity in the brain of hypertensive Dahl salt-sensitive (DSS) rats and the consequences of enhanced nNOS activity. Male DSS rats were fed either a regular (0.4% NaCl) or high-salt (8% NaCl) diet, with or without 0.25% nifedipine, for 4 weeks. The effects of nifedipine, which lowers blood pressure peripherally, on central nNOS were determined by measuring nNOS activity, as well as the number of nNOS-positive neurons in the brain stem and diencephalon. The effects of chronic (12 days) infusion of 7 μg (0.5 μL/h, i.c.v.) S-methyl-L-thiocitrulline (SMTC; a stereoselective competitive nNOS inhibitor) on mean arterial pressure were assessed in conscious DSS rats using a radiotelemetry system. In addition, the number of central nNOS-positive neurons was compared between DSS and salt-insensitive Sprague-Dawley rats. Normalization of blood pressure by nifedipine attenuated the increase in nNOS activity in the brain stem of DSS rats. Chronic i.c.v. infusion of SMTC further enhanced hypertension in DSS rats. Feeding of a high-salt diet increased nNOS-positive neurons in the lateral parabrachial nucleus, rostral ventrolateral medulla and nucleus tractus solitarius of DSS compared with Sprague-Dawley rats, whereas nNOS-positive neurons in the paraventricular nucleus remained downregulated in DSS rats. The results of the present study suggest that hypertension, rather than a high-salt diet, increases central nNOS activity in hypertensive DSS rats to buffer high blood pressure. However, this compensatory response may be insufficient to relieve salt-induced hypertension.
authors.affiliation: Department of Physiology, National Defense Medical College, Tokorozawa, Saitama, Japan. meguth@ndmc.ac.jp
authors.forename: Megumi
authors.initials: M
authors.lastname: Tandai-Hiruma
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kato
authors.forename: Takehito
authors.initials: T
authors.lastname: Kemuriyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohta
authors.forename: Akimasa
authors.initials: A
authors.lastname: Tashiro
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Hagisawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishida
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D013686:Telemetry; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D017673:Sodium Chloride, Dietary; D002956:Citrulline; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D013890:Thiourea; C086717:S-methylthiocitrulline