Effects of nitroglycerin on cardiac function and regional blood flow distribution in conscious dogs

Vatner, Stephen F.; Pagani, M.; Rutherford, John D.; Millard, Ronald W.; Manders, W. T.

doi:10.1152/ajpheart.1978.234.3.h244

Cited by 57 publications

(28 citation statements)

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“…Nitroglycerin is a vasodilator agent that is widely used in the treatment of anginal disease whereas nitroprusside is used in the management of hypertensive emergencies and for afterload reduction in patients with left heart failure and myocardial infarction (1)(2)(3)(4). Although the systemic vascular responses to nitroprusside and nitroglycerin have been intensively investigated (5)(6)(7)(8), the actions of these substances on the pulmonary circulation have received less attention and little, if anything, is known about the effects of these agents on the pulmonary veins (9)(10)(11)(12)(13). Nitroprusside and nitroglycerin have been reported to decrease pulmonary arterial pressure in patients with congestive heart failure (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Vasodilator Responses to Nitroprusside and Nitroglycerin in the Dog

Kadowitz¹,

Nandiwada²,

Gruetter³

et al. 1981

J. Clin. Invest.

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A B S T R A C T. The objective of this study was to determine the direct actions of nitroprusside and nitroglycerin on the pulmonary vascular bed in the intactchest dog. These widely used nitrogen oxide-containing vasodilator agents decreased pulmonary arterial pressure and increased cardiac output without altering left atrial pressure. Reductions in pulmonary arterial pressure and pulmonary vascular resistance were small under resting conditions, but were enhanced when pulmonary vascular tone was elevated by infusion of a stable prostaglandin analog that increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In studies in which pulmonary blood flow to the left lower lobe was maintained constant, nitroprusside and nitroglycerin caused small but significant reductions in lobar arterial and small-vein pressures without significantly affecting left atrial pressure. With constant blood flow, lobar vascular pressures that were reduced in response to the vasodilators were more greatly reduced when lobar vascular resistance was increased by infusion of the prostaglandin analog or serotonin. However, when lobar vascular pressures were elevated by passive obstruction of lobar venous outflow, vasodilator responses to nitroprusside and nitroglycerin were not enhanced. These data suggest that nitroprusside and nitroglycerin decrease pulmonary vascular resistance by dilating intrapulmonary veins and upstream segments. These responses were minimal under control conditions but were enhanced when vascular tone was increased. This vasodilator action is independent of passive factors such as changes in pulmonary blood flow or left atrial pressure and is not secondary to an effect of these agents on the systemic circulation. Pulmonary vasodilator responses to nitroprusside and nitroglycerin were, however, found to be dependent on the existing level of vasomotor tone in the pulmonary vascular bed.

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Section: Introductionmentioning

confidence: 99%

Pulmonary Vasodilator Responses to Nitroprusside and Nitroglycerin in the Dog

Kadowitz¹,

Nandiwada²,

Gruetter³

et al. 1981

J. Clin. Invest.

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“…Nitroprusside, used in this study, reduces directly venous tone (23), therefore causing hypotension by reducing cardiac preload (24) and filling. Previous studies in sheep (2-4) have shown that fetal hemorrhage is associated first with an increase then with a rapid decrease in fetal HR as arterial blood pressure decreases further.…”

Section: Discussionmentioning

confidence: 99%

Autonomic Adjustments to Severe Hypotension in Fetal and Neonatal Sheep

et al. 2001

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In fetal sheep, severe hypotension causes heart rate (HR) slowing. Studies during development have also shown that a reflex bradycardia and hypotension can be elicited after chemostimulation with veratridine and is dependent on the age of the animal. In adults, a vagally mediated depressor reflex characterized by bradycardia, hypotension, and withdrawal of efferent sympathetic activity can be observed after stimulation of chemosensitive or mechanosensitive cardiac receptors with veratridine or in circumstances of reduced cardiac filling. This reflex, known as the Bezold-Jarisch reflex, plays a role in disease states such as myocardial ischemia and hemorrhage. The objectives of our study were to determine whether a sympathoinhibitor depressor reflex, along with the bradycardia, is observed during pharmacologically induced hypotension in fetal and newborn lambs. In both fetal and newborn lambs, HR and renal sympathetic nerve activity (RSNA) initially increased (p Ͻ 0.05) in response to nitroprusside infusion to reach a maximum value. The range (or "plateau") of mean arterial blood pressure over which maximum RSNA was maintained constant before withdrawal of sympathetic tone started to be observed was significantly (p Ͻ 0.05) smaller in fetuses (0.3 Ϯ 0.3 mm Hg) than newborn (6 Ϯ 1 mm Hg) lambs. Similarly, the plateau over which maximum HR was maintained before onset of bradycardia was significantly smaller in fetuses (4 Ϯ 1 versus 11 Ϯ 2 mm Hg). The mean arterial blood pressure level ("threshold") at which a depressor reflex was triggered was significantly (p Ͻ 0.05) lower in fetal than newborn sheep (35 Ϯ 2 versus 53 Ϯ 3 mm Hg for HR and 35 Ϯ 2 versus 57 Ϯ 2 mm Hg for RSNA). The rates of fall (slopes) for both HR and RSNA were also significantly (p Ͻ 0.05) more pronounced in fetuses (1.85 Ϯ 0.27 and 6.08 Ϯ 2.45%/mm Hg) than in newborns (1.21 Ϯ 0.16 and 1.97 Ϯ 0.32%/mm Hg). Bilateral vagotomy significantly increased the plateau of mean arterial blood pressure over which maximum RSNA and HR were maintained constant. Vagotomy also decreased the threshold for both RSNA and HR and the slope of the RSNA response to the nitroprusside infusion in newborn lambs. Results from this study show that activation of the arterial baroreflex during nitroprusside-induced hypotension is followed by withdrawal of sympathetic tone and bradycardia and that this depressor reflex is more pronounced in late-gestation fetuses than newborn lambs and is significantly attenuated after bilateral vagotomy in newborn lambs. (Pediatr Res 49: 56-62, 2001) Abbreviations: AP, amniotic pressure BJ, Bezold-Jarisch HR, heart rate MABP, mean arterial blood pressure RSNA, renal sympathetic nerve activityIn fetal sheep, in contrast to the tachycardic response to moderate hypotension (1, 2), severe hypotension causes HR slowing (2-4). This reflex bradycardia can be observed in response to hemorrhage (2), vena caval obstruction (5, 6), and vasodilator infusion (7). In adults, hypotension and bradycardia can be elicited after stimulation of mechanical or che...

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“…Since continuous dosing of nitrates facilitates the maintenance of a constant high blood concentration, this procedure is routinely used to treat unstable angina or heart failure; however, it is known that nitrate tolerance appears within 24 h with respect to improvement in pulmonary wedge pressure or exercise tolerance (3,5). As a strategy to overcome such tolerance, eccentric dosing has been recommended (9,14).…”

Section: Tolerance To Nitratesmentioning

confidence: 99%

“…With respect to systemic circulation and pulmonary circulation, it has been reported that 24-h administration of nitrates induces nitrate tolerance (3). With respect to their direct actions on coronary circulation, nitrates dilate the coronary arteries (4), increasing coronary blood flow (CBF) (5). In many studies examining nitrate tolerance in patients with ischemic heart disease, improvement in exercise tolerance was used as an index (6), and thus the actions of nitrates on the coronary circulation and the appearance of nitrate tolerance remain unclear in many respects.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Nitrate Tolerance without Reducing Vascular Response during Eccentric Dosing of Nitrates

et al. 2006

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It has been reported that the nitrate tolerance related to continuous dosing of nitrates reduces drug efficacy, and therefore eccentric dosing of nitrates is recommended. In this study, we investigated the appearance of nitrate tolerance related to continuous dosing of nitrates and prevention of nitrate tolerance during eccentric dosing by comparing the grade of coronary dilatation after sublingual nitroglycerin. Of 26 patients with ischemic heart disease who underwent elective cardiac catheterization, 8 patients were continuously administered nitrates, 8 patients were eccentrically administered nitrates, and 10 patients were not treated. We compared the coronary response to sublingual nitroglycerin among the 3 groups. In a coronary vessel without significant stenosis, the coronary vessel area, coronary lumen area, and mean coronary blood flow velocity after sublingual nitroglycerin were measured using intravascular ultrasound (IVUS). In the continuous dosing group, the maximal rate of change in the vessel area after sublingual nitroglycerin was 105 ± 1

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Effects of nitroglycerin on cardiac function and regional blood flow distribution in conscious dogs

Cited by 57 publications

References 0 publications

Pulmonary Vasodilator Responses to Nitroprusside and Nitroglycerin in the Dog

Pulmonary Vasodilator Responses to Nitroprusside and Nitroglycerin in the Dog

Autonomic Adjustments to Severe Hypotension in Fetal and Neonatal Sheep

Inhibition of Nitrate Tolerance without Reducing Vascular Response during Eccentric Dosing of Nitrates

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