Pulmonary Vasodilator Responses to Nitroprusside and Nitroglycerin in the Dog

Kadowitz, Philip J.; Nandiwada, P. A.; Gruetter, Carl A.; Ignarro, Louis J.; Hyman, Albert L.

doi:10.1172/jci110107

Cited by 48 publications

(14 citation statements)

References 27 publications

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“…These data suggest that GTN would be expected to decrease capillary hydrostatic pressure and reduce fluid leak in the lung. The results of the present study extend results of previous studies by showing that ALDH2 plays an important role in the bioactivation of GTN in the pulmonary vascular bed of the rat (28,29).…”

Section: Discussionsupporting

confidence: 91%

“…The results of the present study in the rat and previous studies in the dog show that GTN has significant vasodilator activity in the pulmonary vascular bed and that pulmonary vasodilator responses are enhanced when vasoconstrictor tone is increased (28). In addition, studies in the intact-chest dog under constant flow conditions show that decreases in pulmonary (lobar) arterial pressure in response to intravenous injections of GTN are associated with decreases in small intrapulmonary vein pressure (28). These data suggest that GTN would be expected to decrease capillary hydrostatic pressure and reduce fluid leak in the lung.…”

Section: Discussionsupporting

confidence: 69%

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Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat

Badejo

Hodnette

Dhaliwal

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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PJ. Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat. Am J Physiol Heart Circ Physiol 299: H819 -H826, 2010. First published June 11, 2010; doi:10.1152/ajpheart.00959.2009.-It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was ϳ1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat. mitochondrial aldehyde dehydrogenase; xanthine oxidoreductase; nitric oxide; glyceryl trinitrate; sodium nitrite; sodium nitroprusside; allopurinol; cyanamide; U-46619; N G -nitro-L-arginine methyl ester GLYCERYL TRINITRATE (GTN) and, to a lesser extent, amyl nitrite have been used in the treatment of angina and heart failure for more than a century (4, 5, 38). However, the molecular mechanism by which GTN relaxes vascular smooth muscle is still the subject of current investigation and remains unknown. Although it is well established that nitric oxide (NO) activates soluble guanylyl cyclase, increases cGMP formation, and relaxes vascular smooth muscle, the role of NO release in mediating the vasorelaxant response to GTN is uncertain (11,17,21,26,30,37,39). Although studies in the literature provide evidence that NO is released from GTN, other studies show that NO is not released and suggest that the activation of guanylyl cyclase is mediated by a closely related but not currently identified chemical species with NO-guanylyl cyclase stimulating properties (2, 11, 16, 23, 25, 29 -31, 36, 39). There is substantial evidence in the literature that mitochondrial aldehyde dehydrogenase (ALDH2) plays an i...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 69%

Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat

Badejo

Hodnette

Dhaliwal

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

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“…48 50 The baseline value of characteristic impedance of 49 dynsec-cm-5 that we found was similar to the value of 46 dyn-sec-cm-5 found in a population with pulmonary hypertension secondary to mitral stenosis (normal value was 23 dyn-sec-cm-5).51 The elevated total external and oscillatory power also decreased, reflecting the relatively greater decrease in pressure compared to the smaller increase in flow. This effect is in contrast to the increase in external power response in the systemic vasculature where the flow increase is relatively greater than the decrease in pressure.…”

Section: Implications Of the Studysupporting

confidence: 80%

Effect of nitroprusside on hydraulic vascular loads on the right and left ventricle of patients with heart failure.

et al. 1983

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SUMMARY We studied the effect of nitroprusside on the hydraulic vascular load of the right and left ventricle in seven patients with severe left ventricular failure. At doses of 0.25-0.75 ,ug/kg/min, stroke volume increased progressively from 40.1 to 48.6 ml and left ventricular end-diastolic pressure decreased from 24.5 to 11.2 mm Hg. Accompanying this improvement in left ventricular performance were doserelated decreases in mean ventricular pressures, pulmonic and systemic resistances and the lower-frequency components of input impedance moduli. Characteristic impedance and both total and oscillatory external power were decreased in the pulmonic, but not the aortic, vasculature. We sought to determine the mechanism and magnitude of right ventricular unloading and the dose-response relationship of right relative to left ventricular hydraulic unloading with nitroprusside in patients with severe left ventricular failure. A primary concern was whether this agent, in doses just sufficient to produce a measurable alteration in systemic resistance and left ventricular performance, had a primary effect on right ventricular load through a direct effect on pulmonary vascular resistance and impedance. Methods PatientsWe studied patients with severe, chronic left ventricular failure from various causes. Clinically overt left ventricular congestive heart failure was manifested by pulmonary vascular congestion on chest x-ray, ventricular gallop sounds and recent history of both dyspnea and shortness of breath at rest. Patients who were scheduled to undergo diagnostic cardiac catheterization were asked to participate in the study. Any patient with suspected valvular or congenital heart disease was excluded. From this population, 20 patients were entered into the study after they gave informed consent.

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“…The results of the present study indicate that the vagus in the mid-cervical region in the cat carries efferent fibers innervating lung vessels which have adrenergic and cholinergic terminals, and that, in order to demonstrate a vasodilator response to vagal stimulation, it is necessary to interfere with the integrity of the adrenergic nerves and to enhance vasoconstrictor tone, since the pulmonary vascular bed has little, if any, vasoconstrictor tone under resting conditions (Hyman and Kadowitz, 1979;Hyman et al, 1981;Kadowitz et al, 1981). The physiological significance of the cholinergic dilator system is uncertain at resting tone (Fio 2 0.21) conditions.…”

Section: Discussionmentioning

confidence: 76%

Pulmonary vasodilator responses to vagal stimulation and acetylcholine in the cat.

Nandiwada¹,

Hyman²,

Kadowitz³

1983

Circulation Research

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SUMMARY. Responses to vagal stimulation and acetylcholine were investigated in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow and constant left atrial pressure. Under baseline conditions, electrical stimulation of vagal efferent fibers increases lobar arterial pressure. However, when vasoconstrictor tone was increased, a depressor response was unmasked. The pressor response under baseline conditions and the depressor response under enhanced tone conditions were blocked by phenoxybenzamine and atropine. These data suggest that, in the cat, the vagus is composed of efferent fibers from both the sympathetic and parasympathetic systems. After treatment with 6-hydroxydopamine to destroy the integrity of the sympathetic system, vagal stimulation caused significant frequency-dependent decreases in lobar arterial pressure when lobar vascular tone was increased by infusion of a stable prostaglandin endoperoxide analog or ventilatory hypoxia. Injections of acetylcholine also caused significant dose-related decreases in lobar arterial pressure when lobar vascular resistance was elevated. Depressor responses to vagal stimulation and acetylcholine in 6-hydroxydopamine-treated animals were blocked by atropine and enhanced by physosrigmine. Decreases in lobar arterial pressure in response to vagal stimulation in 6-hydroxydopamine-treated animals with enhanced tone were blocked by hexamethonium, whereas responses to injected acetylcholine were not altered by the ganglionic blocking agent. Decreases in lobar arterial pressure in response to vagal stimulation and acetylcholine were similar when the lung was ventilated and when the left lower lobe bronchus was obstructed. In addition, responses to vagal stimulation were similar when systemic arterial pressure was decreased to the level of pressure in the perfused lobar artery. Responses to acetylcholine were not altered after treatment with 5,8,11,14-eicosatetraynoic acid, a lipoxygenase inhibitor. The present data suggest that the feline pulmonary vascular bed is functionally innervated by cholinergic nerves and that vagal stimulation dilates the pulmonary vascular bed by releasing acetylcholine which acts on muscarinic receptors in pulmonary vessels. (Circ Res 53: 86-95, 1983)

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Pulmonary Vasodilator Responses to Nitroprusside and Nitroglycerin in the Dog

Cited by 48 publications

References 27 publications

Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat

Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat

Effect of nitroprusside on hydraulic vascular loads on the right and left ventricle of patients with heart failure.

Pulmonary vasodilator responses to vagal stimulation and acetylcholine in the cat.

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