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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/m, 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/m. 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.

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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.

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The aim of this study was to evaluate the fibrinolytic system by measurement of fibrinogen, plasminogen, tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) in healthy normotensive subjects and in patients with essential hypertension. A group of 21 healthy normotensive subjects [age, 39.2 +/- 1.8 years; 8 males, 13 females; body mass index (BMI) = 27.9 kg/m] and 42 patients with untreated essential hypertension (age, 47.6 +/- 1.7 years; 19 males, 23 females; BMI = 28.3 kg/m) were studied. Blood samples and clinical measurement were taken between 7 am and 9 am by an observer in a blind fashion. The systolic/diastolic blood pressure of normotensive subjects was 121.3 +/- 2.5/78.4 +/- 1.3 mm Hg and that of hypertensive patients was 166.4 +/- 4.3/102.9 +/- 1.83 mm Hg, measured in the sitting position. Plasma fibrinogen levels in the normotensive and hypertensive individuals were 295.7 +/- 9.4 mg/dL and 305.67 +/- 10.9 mg/dL, respectively (P = 0.456). The corresponding values for plasminogen were 71.4 +/- 3.8% and 89.5 +/- 2.5%, (P = 0.0031), for t-PA were 6.3 +/- 0.5 ng/mL and 7.6 +/- 0.4 ng/mL (P = 0.0487), and for PAI-1 were 46.9 +/- 5.1 ng/mL and 63.0 +/- 5.6 ng/mL (P = 0.0324), respectively. In conclusion, patients with essential hypertension have disequilibrium in the fibrinolytic system with a tendency toward a hypercoagulability state when compared with normotensive subjects. This state could explain, in part, the thrombotic complications that occur with a higher frequency in hypertensive patients as compared with normotensive subjects.

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Con el objetivo de evaluar el efecto de la combinación losartan más hidroclorotiazida (HCTZ) sobre la presión arterial y en la producción de óxido nítrico (ON) en pacientes hipertensos "non dippers", se realizó un estudio prospectivo donde se evaluaron 12 pacientes (6 de cada sexo) con edad promedio de 52.42 ± 2.52 años e hipertensión severa de reciente diagnóstico (PAS/PAD) en la consulta-posición sentada: 188 ± 5.22/116.17 ± 1.22 mmHg). Los pacientes inicialmente fueron evaluados en placebo en forma ciego-simple, por un máximo de 3 semanas, durante ese período fueron examinados semanalmente; luego recibieron la combinación de losartan (100 mg) + HCTZ (25 mg), en una toma diaria durante 12 semanas. Un monitorio de presión arterial durante 24 horas y los niveles séricos y urinarios (24 horas) de ON fueron practicado al final de la etapa placebo y de medicación activa. En la etapa placebo el promedio de la PAS/PAD 24 horas fue de 158.6 ± 4.67/102.2 ± 2.57 mmHg; la presión de pulso (PP) de 56.5 ± 2.70 mmHg y la frecuencia cardiaca (FC) fue de 74.8 ± 1.81/min. El promedio diurno fue 159.3 ± 4.35/103.0 ± 2.50 mmHg; y el promedio nocturno de 154.9 ± 5.33/98.9 ± 3.12 mmHg. La PP diurna era de 56.05 ± 3.05 mmHg y la nocturna de 55.89 ± 3.41 mmHg. Luego de 12 semanas de terapia combinada, el promedio de la PAS/PAD se redujo a 140.3 ± 4.83 (p menor igual 0.001) /90.9 ±3.27 mmHg (p menor igual 0.002); la PP presentó descenso a 49.8 ± 2.46 mmHg (p menor igual 0.006) y la FC pasó a 77.9 ± 2.17 ppm (p menor igual 0.08). La PAS/PAD diurna fue de 135,01 ± 4.37) /88.15 ± 3.10 mmHg (p menor igual 0.002) respectivamente. La PAS/PAD nocturna fue de 140.9 ± 4.62 (p menor igual 0.035)/91.5 ± 3.24 mmHg. (p menor igual 0.05). La PP diurna y nocturna sufrieron reducciones a 49.9 ± 2.36 (p menor igual 0.007) y 50.33 ± 3.06 mmHg (p menor igual 0.05) respectivamente. El ON sérico pasó de 40.89 ± 5.69 uM/L en la etapa placebo a 67.35 ± 6.96 µM/L (p menor igual 0.007) al final de la medicación activa; mientras que la concentración urinaria pasó de 69.71 ± 3.68 uM/L a 79.64 ± 4.25 uM/L (p menor igual 0.16); el clearence urinario de ON no fue modificado significativamente durante la terapia antihipertensiva y pasó de 1.14 ± 0.32 ml/min 1.15 ± 0.14 ml/min (p menor igual 0.9). La combinación losartan (100 mg) más hidroclorotiazida (25 mg) en una toma diaria disminuyó la presión arterial nocturna sin modificar el patrón "non dippers" de pacientes con hipertensión arterial severa

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