title: Basal nitric oxide synthesis in essential hypertension.
abstract: BACKGROUND
  There is indirect evidence that nitric oxide (NO) synthesis in vascular endothelium of patients with hypertension is altered. The aim of this study was to estimate more directly NO production in patients with untreated essential hypertension by measurement of synthesis of inorganic nitrate, which is the end product of NO oxidation in humans. Two separate studies were undertaken in patients with hypertension and appropriate healthy controls.
  
  
  METHODS
  In the first study, ten patients and 13 controls were given a diet containing 82 mumoles nitrate per day for 2 days, with urinary and plasma nitrate measurement and 24 h ambulatory blood pressure monitoring on the 2nd day. In the second study, 11 patients and 11 controls were studied in the postabsorptive state; a bolus of 200 mg L[15N]2 arginine was administered intravenously over 10 min. 24 h ambulatory blood pressure monitoring was done and complete urine collections were made for the next 36 h.
  
  
  RESULTS
  In the first study, 24 h urinary nitrate excretion was lower in the hypertensive patients than in the control group (mean 450 [SEM 37] vs 760 mumoles [77] per 24 h; p < 0.001). There was an inverse correlation between average mean daytime ambulatory blood pressure and nitrate excretion (p = 0.007; r2 = -0.73). In the second study, mean 36 h urinary 15N nitrate excretion was significantly lower in the hypertensive than in the control group (1313 [50] vs 2133 [142] pmoles; p < 0.001). There was an inverse correlation also between average mean daytime ambulatory blood pressure and 24 h urinary 15N nitrate excretion expressed per mmole of creatinine (p = 0.002, r2 = -0.59). In addition, total urinary 15N nitrate excretion in the hypertensive group was significantly higher in women than in men (285 [16] vs 198 [14] micrograms 15N nitrate per kg; p = 0.026).
  
  
  CONCLUSIONS
  These data suggest that whole-body NO production in patients with essential hypertension is diminished under basal conditions. The origin of the NO we measured is not known, and we cannot tell whether the impaired synthesis is primary or secondary to a rise in blood pressure.
authors.affiliation: Department of Clinical Pharmacology, St Bartholomew's, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Forte
authors.forename: M
authors.initials: M
authors.lastname: Copland
authors.forename: L M
authors.initials: LM
authors.lastname: Smith
authors.forename: E
authors.initials: E
authors.lastname: Milne
authors.forename: J
authors.initials: J
authors.lastname: Sutherland
authors.forename: N
authors.initials: N
authors.lastname: Benjamin
mesh_terms: D000328:Adult; D001120:Arginine; D001794:Blood Pressure / Q000502:physiology; D018660:Blood Pressure Monitoring, Ambulatory; D016022:Case-Control Studies; D004032:Diet; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism
chemical_list: D009566:Nitrates; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase