Effect of Enalapril on Exhaled Nitric Oxide in Normotensive and Hypertensive Subjects

Abstract

Abstract-We investigated whether an angiotensin-converting enzyme (ACE) inhibitor increases the production of nitric oxide (NO) in exhaled air in normotensive and hypertensive subjects. In study 1, 8 normotensive male subjects received a single oral dose of enalapril (5 mg) or nitrendipine (10 mg) in a crossover manner. Exhaled air was collected at baseline, and at 2, 4, and 8 hours after administration of the drug. In study 2, 10 normotensive subjects (6 men and 4 women) and 10 hypertensive subjects (6 men and 4 women) received a single oral dose of enalapril (5 mg). Exhaled air was collected at baseline and at 2 and 4 hours after administration of the drug. In study 1, enalapril significantly increased the NO release rate from the lung in normotensive subjects (36.9Ϯ5.1 pmol/s at baseline versus 58.3Ϯ7.3 pmol/s at 4 hours, PϽ0.01). Nitrendipine did not change the NO release rate. In study 2, enalapril significantly increased the release of NO from the lung in normotensive subjects (40.4Ϯ6.0 pmol/s at baseline versus 70.3Ϯ11.4 pmol/s at 4 hours, PϽ0.01) but not in hypertensive subjects. ACE inhibition increased NO production from the lung in normotensive subjects but not in hypertensive patients. The reduction of angiotensin II production and/or the accumulation of bradykinin in the pulmonary tissue may be responsible for increased NO production in components of the lung, such as the pulmonary vascular endothelium, bronchial epithelial cells, macrophages, nasopharyngeal cells, and neurons. However, the effects of ACE inhibition on NO production from the lung differ between hypertensive subjects and normotensive subjects. Key Words: angiotensin Ⅲ bradykinin Ⅲ hypertension, essential Ⅲ nitric oxide E ndothelium-derived relaxing factor (EDRF) has been identified as nitric oxide (NO), a potent vasodilator. 1 The attenuated endothelium-dependent vasodilation in patients with essential hypertension 2 may be largely mediated by a decrease in the release or activity of NO. Decreased endothelial NO is considered to be either a cause or a consequence of hypertension.NO is a highly unstable substance with a plasma half-life of only a few seconds 3 ; therefore, its direct measurement is difficult, particularly in vivo. Endogenously produced NO is assessed by measuring the serum levels of NOx, the products of NO metabolism, or by measuring endogenous NO present in expired air. The presence of endogenous NO in exhaled air has been demonstrated in humans. 4 The cellular source of exhaled NO is not known, but it has been proposed that all NO synthase isoforms in the respiratory system contribute to NO release. 5 Therefore, the amount of NO in expired air is an appropriate indicator of endogenously produced NO in the lung. We recently developed a method for measuring NO in exhaled air. 6 Angiotensin-converting enzyme (ACE) inhibitors improve impaired endothelium-dependent vascular relaxation in rats, 7 but this effect of ACE inhibitors is not always demonstrated in humans. 8,9 However, it has not yet been established whether or...

Bronchoalveolar lavage, sputum and exhaled clinically relevant inflammatory markers: values in healthy adults

“…They include sex and sexual hormones, body weight and age, circadian changes of respiratory function in health and disease, caffeine and alcohol, meals rich in nitrate, genetic background for some enzymes, upper respiratory tract infection, exercise, drugs (including inhibitors of NO synthases) and of course smoking [46,[54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73]. Moreover, FeNO levels in healthy subjects are influenced by atopy, i.e.…”

Non‐invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L‐arginine and sublingual nitroglycerin

“…Increased alveolar NO concentration has also been reported in subjects with liver cirrhosis [50], presumably as a result of increased endothelial NO production [51]. In addition, the administration of the ACE‐inhibitor enalapril has increased NO level in exhaled air, which was thought to reflect enhanced NO release from the capillary endothelium [52]. Since inhaled salbutamol is not likely to influence NO production in the alveolar epithelium or change NO permeability of the alveolar wall, the present findings suggest that salbutamol inhalation increased NO release from the capillary endothelium.…”

Nitrite exhaled breath condensate study in patients undergoing cardiopulmonary bypass cardiac surgery

“…The biochemical and pharmacological effects of NO 3 -are identical to those of the NO-derived relaxing factor from the endothelium; therefore, isosorbide dinitrate may promote NO bioavailability. According to Sumino et al [9], because the measurement of exhaled NO is directly derived from the lung, it is possible that ACE inhibitors cause larger NO release in the latter organ compared with the serum NO x level in the peripheral venous blood. It is possible that NO production in the systemic circulation is also promoted by ACE inhibition, but this change is so small that NO x is rapidly excreted in urine without apparent alterations in the NO x serum level.…”

“…In other words, it is possible that ACE inhibition causes further increase in NO released by the lungs compared with NO x levels present in the plasma from peripheral venous blood. In addition, it can be speculated that the reduced production of angiotensin II and / or the accumulation of bradykinin in the lung tissue may be responsible for the larger NO production in lung components such as the pulmonary vascular endothelium, bronchial epithelial cells, macrophages, and neurons in the nasopharynx [9].…”