Role of NO pathway, calcium and potassium channels in the peripheral pulmonary vascular tone in dogs

Abstract

Because hypoxic pulmonary vasoconstriction occurs mainly in the small pulmonary arteries, the authors investigated the effects of drugs acting on the nitric oxide (NO) pathway and the calcium and potassium channels in the peripheral pulmonary circulation, without interference with the overall pulmonary or systemic circulation.Mixed venous blood was infused in wedged areas to study the pressure/¯ow relationship and to compute peripheral pulmonary vascular resistance (PPVR). The authors studied the effects of N v -nitro-l-arginine methyl ester (l-NAME), an NO synthase inhibitor, sodium nitroprusside (SNP, an NO donor), the calcium channel blockers verapamil, nifedipine and nicardipine, and the potassium channel opener levcromakalim, during normoxia and acute mild normocapnic hypoxia.In the peripheral pulmonary circulation, l-NAME caused an increase in PPVR during normoxia (z95%; p<0.001) and hypoxia (z60%; p<0.01). Following the increase by l-NAME, SNP decreased PPVR during normoxia (-24%; p<0.05) and hypoxia (-23%; p<0.05). Verapamil, nifedipine and nicardipine did not modify PPVR during normoxia but during hypoxia they decreased PPVR (-28%, nonsigni®cant; -27%, p<0.01 and -33%, p<0.05, respectively). Levcromakalim did not modify PPVR during normoxia or hypoxia.In conclusion, the nitric oxide pathway and voltage-dependent calcium channels, and not adenosine triphosphate sensitive potassium channels, play an important role in the control of peripheral pulmonary circulation in dogs. Segmental differences in vasomotor reactivity are well documented in the pulmonary vasculature. Hypoxia causes sustained constriction in resistance pulmonary arteries [1] while causing a biphasic response in conduit pulmonary arteries [2]. Investigations on resistance vessels have been performed mainly in vitro on small isolated pulmonary artery rings. Some authors investigated the relationship between pressure and¯ow in the pulmonary circulation in vivo for a lobe in situ [3], but the preparation included predominantly conduit vessels and the¯ow changes induced modi®cations of other variables. Because alveolar hypoxia is an important regulator of pulmonary vascular tone and causes vasoconstriction mainly in small pulmonary arteries, the authors studied, in vivo, the pharmacology of the vasomotor response of the peripheral pulmonary circulation, during normoxia and mild acute hypoxia.Under physiological conditions, the vasodilator nitric oxide (NO) is continually released by endothelial cells and regulates organ and perfusion pressure and¯ow [4]. Endogenous NO may contribute to the maintenance of normal pulmonary vasomotor tone. Pulmonary vascular tone is also regulated by the activity of calcium and potassium channels, and the links between activation of both calcium and potassium channels and NO-induced relaxation in the proximal part of the pulmonary artery have been emphasized, in vitro [5]. Various inhibitors of NO synthase (NOS) have been shown to increase the normoxic pulmonary vascular tone in some [6,7] but not in all...

Differences in selected blood parameters between brachycephalic and non-brachycephalic dogs

“…Our data reflected higher levels of RNO in the plasma of BC dogs compared to the NC group ( Figure 1A ). NO release in response to acute or chronic hypoxia induces vasodilatation in humans ( 74 ) and dogs ( 75 , 76 ). The pattern of changes in NO production during chronic intermittent hypoxia is more complex.…”