Effect of Losartan Plus Hydrochlorothiazide on Nitric Oxide Status in ‘Nondipper’ Hypertensive Patients

The objective of this study was to investigate the effects of losartan (100 mg) plus hydrochlorothiazide (HCTZ; 25 mg) on nitric oxide (NO) production and blood pressure (BP) in "nondipper" severe hypertensive patients. Twelve hypertensive "nondipper patients" (6 of each gender) with sitting systolic/diastolic BP of 188.0 +/- 5.2/116.2 +/- 1.2 mm Hg were studied by 24-hour ambulatory blood pressure monitoring (ABPM) after daily administration of 100 mg losartan plus 25 mg HCTZ for a period of 12 weeks. Office and mean 24-hour, as well as mean awake- and sleep-time systolic/diastolic BP, serum NO levels, and urinary excretion of NO were measured after the placebo period (3 weeks) and after 12 weeks of therapy. At the end of the 12-week treatment period, the mean 24-hour systolic/diastolic BP decreased significantly from 158.6 +/- 4.7/102.2 +/- 2.6 mm Hg (placebo period) to 140.3 +/- 4.8/90.9 +/- 3.3 mm Hg (P = 0.001/< or = 0.002). The mean BP (systolic/diastolic) during the waking period was reduced from 159.3 +/- 4.4/103.0 +/- 2.5 mm Hg to 135.0 +/- 4.4/88.2 +/- 3.1 (P < or = 0.007/P < or = 0.002), whereas the mean BP (systolic/diastolic) during the sleeping hours changed from 154.9 +/- 5.3/98.9 +/- 3.1 to 140.9 +/- 4.6 (P = 0.035)/91.7 +/- 3.2 mm Hg (P = 0.035/P = 0.051). Serum NO levels increased from 40.89 +/- 5.69 microM/L (placebo period) to 67.35 +/- 6.96 microM/L (posttreatment; P < or = 0.007), whereas the 24-hour urinary NO excretion did not change significantly (69.71 +/- 3.68 microM/L [placebo period] vs 79.64 +/- 4.25 microM/L [posttreatment]; P < or = 0.16). Urinary clearance of NO also did not change. Serum NO levels increased significantly without a significant change in urinary NO excretion. BP was significantly reduced but without modifying the nondipper pattern in these patients.