Hemodynamic and hormonal effects of high-dose transdermal nitroglycerin in patients with chronic congestive heart failure

Elkayam, Uri; Roth, Arie; Henriquez, B.; Weber, Laura; Tonnemacher, David; Rahimtoola, Shahbudin H.

doi:10.1016/0002-9149(85)91184-1

Cited by 58 publications

(13 citation statements)

References 20 publications

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“…However, substantial attenuation of the acute hemodynamic effects of organic nitroesters has been described within 4 to 8 hours of continuous intravenous administration in previous studies of nitrate tolerance. 13,14 The mechanisms that mediate the vascular effects produced by systemic administration of NTG at therapeutic doses are likely to be more complex than that reported in the present study, which involved regional administration of NTG at 10`9 mol/L. Nevertheless, our results suggest that the hemodynamic effects of NTG may, in part, result from an interaction with the vascular endothelium.38-40 Endothelium-dependent vasodilation, which is depressed in the basal state in patients with CHF, also is likely to be abnormal during physiological states of increased shear stress, such as during intense exercise.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in patients with congestive heart failure.

et al. 1994

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NTG, when administered intra-arterially for 20 minutes at a dose that does not affect resting forearm blood flow, specifically increased the vasodilatory response to intra-arterial administration of Ach in patients with CHF but not in normal subjects. The vasodilatory response to Ach was consistently enhanced by low-dose NTG throughout a 12-hour period. The vasodilating effects of organic nitroesters on the peripheral vasculature of patients with CHF may result in part from an interaction with the vascular endothelium.

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Section: Discussionmentioning

confidence: 99%

Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in patients with congestive heart failure.

et al. 1994

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“…Together with the difference in the maximum absolute change in the mean right atrial pressure between both treatment days (Figure 4), this may suggest early attenuation of venodilator efficacy in our patient population. Early attenuation of vasodilator efficacy is an important issue with a number of vasodilators [3], such as prazosin, nitroglycerin, and nitrates [9][10][11][12][13][14][15][16] and may relate to reflex vasoconstrictory forces with or without neurohumoral activation [17][18][19][20], enhanced salt and water reabsorption [21], or a drug-specific effect [22]. Late hemodynamic tolerance and lack of a clinical benefit of fiosequinan may occur in patients with an activated renin-angiotensin system [23].…”

Section: Reproducibility and Accumulation Of Hemodynamic Effects Aftementioning

confidence: 99%

Duration and reproducibility of initial hemodynamic effects of flosequinan in patients with congestive heart failure

Bartels

Remme

Wiesfeld

et al. 1990

Cardiovasc Drug Ther

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The duration and reproducibility of hemodynamic effects of flosequian, a direct-acting, balanced-type vasodilator, were studied in 19 heart failure patients (NYHA class 3.0 +/- 0.7) receiving 100 mg orally (day 1), placebo (day 2), and again 100 mg (day 3). Flosequinan immediately reduced systemic and pulmonary resistance (23% and 35%, respectively, at 60-90 minutes postdrug) and decreased pulmonary wedge, right atrial, mean pulmonary artery, and mean arterial pressure by 38%, 50%, 25%, and 7%, respectively. Concomitantly, cardiac output, and stroke volume and work increased by 26%, 20%, and 22%, respectively. Most hemodynamic effects persisted for 48 hours. In contrast, changes in pulmonary wedge and arterial pressures, stroke volume, and stroke work only lasted for 2-12 hours. Maximum absolute changes on day 3 were generally comparable with first-dose effects with, again, long-lasting effects on systemic resistance and cardiac output. However, changes in pulmonary artery, wedge, and resistance were significantly shorter than after first dose administration. These data indicate sustained and reproducible arterial dilating effects of flosequinan, but less pronounced and shorter lasting pulmonary arterial and venodilator properties.

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“…Mechanisms proposed for nitrate tolerance include impaired nitrate biotransformation [5], intracellular sulfhydryl group depletion [6], neurohumoral counterregulation [7], overproduction of reactive oxygen species [8], and alteration in the activities of the key enzymes which regulate cGMP levels, such as guanylate cyclase and cyclic nucleotide phosphodiesterase (PDE) [9]. …”

Section: Introductionmentioning

confidence: 99%

Differential Expression of Genes from Nitrate-Tolerant Rat Aorta

Yan

Kim

et al. 2002

J Vasc Res

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Organic nitrates act as vasodilators and have long been used for treatment of cardiovascular diseases. However, the therapeutic effect of nitrates is limited by induction of nitrate tolerance which is associated with endothelial dysfunction and enhanced vasoconstriction. Multiple mechanisms cause nitrate tolerance including alterations in gene expression. To identify genes whose expression is altered due to chronic treatment with nitroglycerin (NTG), nitrate-tolerant rats were made by infusion of NTG for 3 days (10 µg/kg/min) using an osmotic minipump. We constructed a PCR-selected cDNA subtracted library from NTG-treated and vehicle-treated rat aortas. Screening of ∼500 clones in the subtracted library showed that four genes were regulated by NTG treatment. Specifically, mRNA levels of β-globin, tropoelastin, gelsolin and a small G protein were confirmed to be upregulated consistently by NTG treatment. These identified genes may play important roles in the development of nitrate tolerance and represent promising candidates to understand the mechanisms of nitrate tolerance and endothelial dysfunction in the vasculature.

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Hemodynamic and hormonal effects of high-dose transdermal nitroglycerin in patients with chronic congestive heart failure

Cited by 58 publications

References 20 publications

Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in patients with congestive heart failure.

Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in patients with congestive heart failure.

Duration and reproducibility of initial hemodynamic effects of flosequinan in patients with congestive heart failure

Differential Expression of Genes from Nitrate-Tolerant Rat Aorta

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