BASAL NITRIC-OXIDE SYNTHESIS IN ESSENTIAL-HYPERTENSION

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 pati ents with untreated essential hypertension by measurement of synthesis of inorganic nitrate, which is the end product of NO oxidation in hum ans. Two separate studies were undertaken in patients with hypertensio n and appropriate healthy controls.(1) Methods In the first study, ten patients and 13 controls were given a diet containing 82 mu moles nit rate per day for 2 days, with urinary and plasma nitrate measurement a nd 24 h ambulatory blood pressure monitoring on the 2nd day. In the se cond study, 11 patients and 11 controls were studied in the postabsorp tive state; a bolus of 200 mg L-[N-15](2) arginine was administered in travenously over 10 min. 24 h ambulatory blood pressure monitoring was done and complete urine collections were made for the next 36 h. Find ings In the first study, 24 h urinary nitrate excretion was lower in t he hypertensive patients than in the control group (mean 450 [SEM 37] vs 760 mu moles [77] per 24 h; p<0001). There was an inverse correlati on between average mean daytime ambulatory blood pressure and nitrate excretion (p=0.007; r(2)=-0.73). In the second study, mean 36 h urinar y N-15 nitrate excretion was significantly lower in the hypertensive t han in the control group (1313 [50] vs 2133 [142] pmoles; p<0.001). Th ere was an inverse correlation also between average mean daytime ambul atory blood pressure and 24 h urinary N-15 nitrate excretion expressed per mmole of creatinine (p=0.002, r(2)=-0.59). In addition, total uri nary N-15 nitrate excretion in the hypertensive group was significantl y higher in women than in men (285 [16] vs 198 [14] mu g N-15 nitrate per kg; p=0.026). Interpretation These data suggest that whole-body NO production in patients with essential hypertension is diminished unde r 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.