title: Sodium sensitivity and sympathetic nervous system in hypertension induced by long-term nitric oxide blockade in rats.
abstract: 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 NG-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. NG-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. NG-Nitro-L-arginine methyl ester-induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites NO2- and NO3- 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 NO2- and NO3- 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.
authors.affiliation: Second Department of Internal Medicine, School of Medicine, Kagawa Medical University, Japan. yuasa@chs.pref.kagawa.jp
authors.forename: S
authors.initials: S
authors.lastname: Yuasa
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Hitomi
authors.forename: M
authors.initials: M
authors.lastname: Hashimoto
authors.forename: H
authors.initials: H
authors.lastname: Fujioka
authors.forename: H
authors.initials: H
authors.lastname: Kiyomoto
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: T
authors.initials: T
authors.lastname: Shoji
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Miki
authors.forename: A
authors.initials: A
authors.lastname: Miyatake
authors.forename: K
authors.initials: K
authors.lastname: Mizushige
authors.forename: H
authors.initials: H
authors.lastname: Matsuo
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced* / Q000652:urine; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009573:Nitrites / Q000652:urine; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002395:Catecholamines; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D012964:Sodium; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester