5.3 INORGANIC NITRITE, CONDUIT ARTERIES & CENTRAL BLOOD PRESSURE

Abstract

Background. Organic nitrates (e.g. nitroglycerin) are highly selective dilators of muscular conduit arteries. By contrast, the endogenous inorganic nitrite anion (NO2−) is thought to be a hypoxia-dependent dilator of small resistance arterioles, via its reduction to vasodilating nitric oxide (NO) by deoxyhaemoglobin. Objective. To establish selectivity of nitrite for resistance versus conduit arteries. Methods and Results A series of forearm blood flow (FABF) studies were performed in healthy volunteers. Intra-brachial sodium nitrite (8.7 μmol/min) markedly increased radial artery diameter (assessed using ultrasound) by 37.6 ± 9.7% (P < 0.001), with HbO2 ∼99%. Furthermore, nitrite (0.087–87 μmol/min) displayed similar selectivity as nitroglycerin (0.003–1 μg/min) for conduit arteries, compared to resistance arterioles (FABF). Intravenous administration of sodium nitrite (8.7 μmol/min) dilated the contralateral radial artery by 10.7 ± 1.8% (P < 0.01) and lowered central systolic blood pressure (BP) by ~12mmHg from 98.3 ± 12.3 to 86.7 ± 15.1 mmHg (P = 0.02) without any change in peripheral BP; nitrite also reduced augmentation index and pulse wave velocity. In contrast to nitrite’s effects on FABF, induction of hypoxia (breathing 12% O2) paradoxically inhibited nitrite-induced dilatation of the radial artery to a similar extent as hyperoxia/ breathing 100% O2 (both P < 0.001 compared to normoxia). Conclusions. Contrary to expectation, inorganic nitrite is a normoxia-dependent selective conduit artery dilator with similar selectivity to nitroglycerin. A specific advantage of nitrite is that it lacks the problems of development of tolerance and endothelial dysfunction, which limit the efficacy of organic nitrates. The selective central BP-lowering effects of nitrite have therapeutic potential to reduce cardiovascular events.