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High blood pressure enhances brain stem neuronal nitric oxide synthase activity in Dahl salt‐sensitive rats
Author(s) -
TandaiHiruma Megumi,
Kato Kazuo,
Kemuriyama Takehito,
Ohta Hiroyuki,
Tashiro Akimasa,
Hagisawa Kohsuke,
Nishida Yasuhiro
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12049
Subject(s) - nifedipine , neuronal nitric oxide synthase , medicine , endocrinology , blood pressure , chemistry , nitric oxide synthase , premovement neuronal activity , nitric oxide , medulla oblongata , central nervous system , biology , calcium , neuroscience
Summary 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.