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.

Angiotensin II receptor blockers represent a class of effective and well tolerated orally active antihypertensive drugs. Activation of AT(1) receptors leads to vasoconstriction, stimulation of the release of catecholamines and antidiuretic hormone and promote growth of vascular and cardiac muscle. AT(1) receptor blockers antagonise all those effects. Losartan was the first drug of this class marketed, shortly followed by valsartan, irbesartan, telmisartan, candesartan, eprosartan and others on current investigation. All these drugs have the common properties of blockading the AT(1) receptor thereby relaxing vascular smooth muscle, increase salt excretion, decrease cellular hypertrophy and induce antihypertensive effect without modifying heart rate or cardiac output. Most of the AT(1) receptor blockers in use controlled blood pressure during the 24 h with a once-daily dose, without evidence of producing tolerance to the antihypertensive effect and being with low incidence of side effects even at long term use. Monotherapy in mild-to-moderate hypertension controls blood pressure in 40 to 50% of these patients; when a low dose of thiazide diuretic is added, 60-70% of patients are controlled. The efficacy is similar to angiotensin-converting enzyme (ACE) inhibitors, diuretics, calcium antagonists and beta-blocking agents. AT(1) receptor blockers are specially indicated in patients with hypertension who are being treated with ACE inhibitors and developed side effects such as, cough or angioedema. The final position in the antihypertensive therapy in this special population and other clinical situations, such as left ventricular hypertrophy, heart failure, diabetes mellitus and renal disease, has to be determined in large prospective clinical trials, some of which are now being conducted and seem promising.

Calcium antagonists are effective in hypertensive patients of all ethnic groups, irrespective of age, dietary salt intake, salt-sensitivity status or plasma renin activity profile. Some prospective studies show that the calcium antagonists, nifedipine GITS and nitrendipine, reduce cardiovascular morbidity and mortality at least to the same extent as the diuretics. Other prospective studies are in progress to evaluate the effect of calcium antagonists on cardiovascular morbidity and mortality, and the progression of atherosclerosis in hypertensive patients. Calcium antagonists, especially the highly lipophilic amlodipine, lacidipine and nisoldipine, are shown to possess antioxidant properties. These drugs reduce the oxidation of LDL and its influx into the arterial wall, and reduce atherosclerotic lesions in animals. Platelet production of malondialdehyde, a marker of oxygen free radical formation, is suppressed by amlodipine, lacidipine or nifedipine in hypertensive patients. New evidence from long-term clinical trials of calcium antagonists indicates that these drugs can reduce the rate of progression of atherosclerosis in hypertensive and coronary heart disease patients. In the Regression Growth Evaluation Statin Study (REGRESS), co-administration of calcium antagonist, amlodipine or nifedipine with pravasatin caused a significant reduction in the appearance of new angiographic lesions. In the Verapamil in Hypertension and Atherosclerosis Study (VHAS), verapamil was more effective than chlorthalidone in promoting regression of thicker carotid lesions in parallel with a reduction in the incidence of cardiovascular events. In the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), amlodipine slowed the progression of early coronary atherosclerosis in patients with coronary artery disease. In a subprotocol of the Intervention as a Goal in the Hypertension Treatment (INSIGHT) study, nifedipine GITS significantly decreased intima-media thickness as compared to co-amilozide (hydrochlorothiazide + amiloride). Preliminary results of the European Lacidipine Study on Atherosclerosis (ELSA) show that lacidipine reduced the intima-media thickness progression rate as compared to atenolol. Thus, selective calcium antagonists are potential antiatherosclerotic agents.

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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.