Jaime Guerrero

Nitric oxide and malondialdehyde in human hypertension

Nitric oxide (NO), a multifunctional effector molecule that plays a central role in the maintenance of vascular homeostasis, regulates vascular tone and inhibits platelet and leukocyte adhesion to endothelial cells. NO status is related to the endothelial function. Patients with hypertension have lower levels of NO, increased free radical production, higher oxidative stress, augmented platelet aggregation, and a change in the arachidonic acid cascade metabolism, all leading to the acceleration of the atherosclerotic process. The study subjects included a group of 21 normotensive healthy subjects (8 males and 13 females) with a mean age of 39.2 ± 1.8 years and a body mass index of 27.9 kg/m2, and another group of 42 patients (19 males and 23 females) with untreated essential hypertension with a mean age of 47.6 ± 1.7 years and a body mass index of 28.3 kg/m2. Serum levels and urinary excretion of NO determined as combined nitrate/nitrite (NOx) and serum malondialdehyde (MDA) concentrations were measured in the 2 groups of subjects. The serum levels and 24-hour urinary excretion of NOx were significantly higher and the renal clearance of NO was lower in the normotensive group than in the hypertensive patients, indicating decreased NO status in hypertension. There was a negative correlation between serum NO levels and mean arterial pressure, suggesting that a decrease in NO availability is related to increase in blood pressure. Serum concentrations of MDA were higher in the hypertensive patients as compared with the normotensive individuals, suggesting increased oxidative stress in hypertensive patients. These results are in agreement with previous studies showing decreased NO and increased oxidative stress in hypertension. In conclusion, patients with essential hypertension as compared with normotensive individuals have lower NO status, which may contribute to the endothelial dysfunction in hypertension. Increased serum malondialdehyde in hypertensives suggests an association between increased oxidative stress with higher blood pressure.

Effect of losartan therapy on endothelial function in hypertensive patients.

The aim of the study was to evaluate the effect of losartan therapy on endothelial function by measuring serum nitric oxide (NO) levels and urinary excretion of NO in patients with essential hypertension. A group of 30 untreated stage 2 hypertensive patients (15 males and 15 females; age, 51.3 ± 1.5 years) were included in the study. Office systolic and diastolic blood pressure (BP) was measured by using a mercury sphygmomanometer according to phase I and V of Korotkoff sounds. NO levels in serum and 24-hour urine were determined at baseline and after 6 weeks of daily dosing with losartan (50-100 mg). Losartan therapy resulted in a significant fall in systolic/diastolic BP (from 169.7 ± 4.1/105 ± 1.8 mm Hg at baseline to 146 ± 2.7/91 ± 1.9 mm Hg at the end of losartan treatment; P < 0.001). The therapy also caused significant increases in both serum NO level (32.74 ± 3.01 μM/L at baseline versus 79.04 ± 5.17 μM/L; P < 0.001 after therapy) and urinary NO excretion (58.21 ± 3.72 μM/L at baseline versus 113.21 ± 8.63 μM/L; P < 0.001 after therapy). Losartan therapy also reduced serum malondialdehyde (MDA), which is a measure of oxidative stress, by 0.201 nM (15.3%; P = 0.009). Losartan at a dose of 50 to 100 mg per day was effective in reducing elevated BP. The increase in serum NO levels and urinary NO excretion and a decrease in serum MDA levels by losartan treatment indicate a reduction in oxidative stress and enhances NO availability, both of which improve endothelial function. Thus, losartan therapy improves endothelial function in hypertensive patients with essential hypertension.

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/≤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 ≤ 0.007/P ≤ 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 μM/L (placebo period) to 67.35 ± 6.96 μM/L (posttreatment; P ≤ 0.007), whereas the 24-hour urinary NO excretion did not change significantly (69.71 ± 3.68 μM/L [placebo period] vs 79.64 ± 4.25 μM/L [posttreatment]; P ≤ 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.