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Sodium Sensitivity And Sympathetic Nervous System In Hypertension Induced By Long‐Term Nitric Oxide Blockade In Rats
Author(s) -
Yuasa Shigekazu,
Li Xiuping,
Hitomi Hirofumi,
Hashimoto Mayuko,
Fujioka Hiroshi,
Kiyomoto Hideyasu,
Uchida Kouichi,
Shoji Tetsuo,
Takahashi Norihiro,
Miki Shigehiro,
Miyatake Akira,
Mizushige Katsufumi,
Matsuo Hirohide
Publication year - 2000
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 - 10.1046/j.1440-1681.2000.03197.x
Subject(s) - nitric oxide , sympathetic nervous system , endocrinology , blood pressure , medicine , sodium , chemistry , excretion , organic chemistry
SUMMARY 1. Pharmacological inhibition of nitric oxide (NO) synthesis is known to produce acute and chronic hypertension in many animal species, but the underlying mechanisms mediating the hypertension are not completely understood. In particular, the pathogenetic roles of sodium sensitivity and the sympathetic nervous system in this model of hypertension are controversial. The present study was designed to test the hypothesis that long‐term administration of the NO synthesis inhibitor N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME) to male Sprague‐Dawley rats would produce a sodium‐sensitive hypertension and that the enhanced activity of the sympathetic nervous system in this type of hypertension contributes to the sodium sensitivity. 2. N G ‐Nitro‐ L ‐arginine methyl ester was added to drinking fluid for 8 weeks at a concentration of 16 mg/dL. Rats received tap water for the first 4 weeks of the study and were then divided into two groups and placed on either a normal or high sodium intake (ingestion of either tap water or 0.9% NaCl, respectively). Awake systolic blood pressure was measured by the tail‐cuff method every week. Urinary excretion rates of the stable NO metabolites and catecholamines during NO synthesis inhibition were examined. 3. Long‐term administration of L ‐NAME produced a marked and sustained elevation in arterial pressure without altering urine flow, or sodium excretion rate. N G ‐Nitro‐ L ‐arginine methyl ester‐induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites NO 2 – and NO 3 – and was aggravated when rats drank 0.9% NaCl in place of tap water. Urinary excretion of adrenaline and noradrenaline, but not dopamine, in L ‐NAME‐treated rats increased significantly within the first week of the study compared with control rats. L ‐Arginine (2 g/dL in drinking fluid) completely reversed the elevation of arterial pressure as well as the decrease in urinary NO 2 – and NO 3 – excretion and the increased urinary excretion of catecholamines associated with L ‐NAME treatment by 3 weeks of concomitant administration. 4. These results suggest that long‐term inhibition of NO synthesis produces a sodium‐sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.