Acute haemodynamic effects of cromakalim in patients with angina pectoris.

Thomas, P. C.; Dixon,; Winterton, S J; Sheridan, Desmond J.

doi:10.1111/j.1365-2125.1990.tb03643.x

Cited by 23 publications

(13 citation statements)

References 9 publications

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“…This discrepancy between the concentrations of chemicals required to produce effects in vivo and in vitro is also seen with others agents, for example the potassium channel opener chromakalin. This reduces systolic arterial pressure and systemic vascular resistance in vivo at concentrations of 2–3 × 10 −8 M (Thomas et al 1990). In vitro these vasodilator effects are seen at 1 × 10 −6 M to 1 × 10 −5 M (Bray et al 1991).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the vasodilatory action of testosterone in the human pulmonary circulation

Smith

Bennett²,

Jones³

et al. 2008

VHRM

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Aim:To assess for the first time the vasodilatory effect of testosterone in the human pulmonary circulation utilizing both isolated human pulmonary arteries and isolated perfused human lungs. In addition, a secondary aim was to determine whether there was any difference in the response to testosterone dependant upon gender.Methods:Isolated human pulmonary arteries were studied by wire myography. Vessels were preconstricted with U46619 (1 nM–1 μM) prior to exposing them to either testosterone (1 nM–100 μM) or ethanol vehicle (<0.1%). Isolated lungs were studied in a ventilated and perfused model. They were exposed to KCl (100 mM), prior to the addition of either testosterone (1 nM–100 μM) or ethanol vehicle (<0.1%).Results:Testosterone caused significant vasodilatation in all preparations, but a greater response to testosterone was observed in the isolated perfused lungs, 24.9 ± 2.2% at the 100 μM dose of testosterone in the isolated pulmonary arteries compared to 100 ± 13.6% at the 100 μM dose in the isolated perfused lungs. No significant differences in the response to testosterone were observed between sexes.Conclusion:Testosterone is an efficacious vasodilator in the human pulmonary vasculature and this is not modulated by patient sex. This vasodilator action suggests that testosterone therapy may be beneficial to male patients with pulmonary arterial hypertension.

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Section: Discussionmentioning

confidence: 99%

Characterization of the vasodilatory action of testosterone in the human pulmonary circulation

Smith

Bennett²,

Jones³

et al. 2008

VHRM

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“…Investigations in man also suggest K+ channel openers to be primarily arteriolar vasodilators (Thomas et al 1990). In healthy men, pinacidil was found to induce vasodilatation of both small and large arteries, leading to a moderate lowering of blood pressure and to stimulation of the reninangiotensin and sympathetic nervous systems (Thuillez et al 1991).…”

Section: Side Effects Of K + Channel Openersmentioning

confidence: 99%

Clinical Pharmacology of Potassium Channel Openers

Andersson

1992

Pharmacology & Toxicology

138

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Opening of K+ channels in cell membranes with resulting increase in K+ conductance, shifts the membrane potential in a hyperpolarizing direction towards the K+ equilibrium potential. Hyperpolarization reduces the opening probability of ion channels involved in membrane depolarization and excitation is reduced. K+ channel openers are believed to hyperpolarize smooth muscle cells by a direct action on the cell membrane. The best known members of the group are cromakalim, nicorandil and pinacidil, but several new compounds are being evaluated. In addition, it has recently been shown that also clinically well-known drugs like, e.g. diazoxide and minoxidil exhibit K+ channel opening properties. Nicorandil and new compounds containing nitro groups have a dual mechanism of action, also activating guanylate cyclase, an effect that contributes to their cardiovascular effect profile. K+ channel openers have a wide range of effects. Some of their properties and actions are summarized, and their present applications and/or potential for future application, in e.g. hypertension, angina pectoris, asthma, bladder instability, and several other disorders are discussed. It is concluded that K+ channel openning represents an interesting pharmacological principle with many potential clinical applications. However, most available drugs do not seem to have a sufficient tissue selectivity to be useful therapeutic alternatives. Before the potential of the new members of the group on clinical trials can be properly evaluated, clinical experiences are needed.

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“…However, it is well described that conductance vessels such as the ones used in ex vivo relaxation studies frequently require higher drug concentrations to elucidate effects, as compared to the concentrations needed to act on smaller, resistance-type vessels in vivo. 45 Despite this minor limitation, the PA ring model is considered an excellent tool for mechanistic vasoreactivity studies, since it (1) eliminates potentially confounding effects of extravascular influences on vasomotor tone (e.g., circulating mediators, neural activity) and (2) allows for evaluation of influences that are localized to the vessel wall (e.g., endothelium-derived relaxing and/or contracting factors, as investigated in our study). 46 Third, we were unable to decipher the exact mechanisms of sitaxsentan-induced improvements in endothelium-independent PA vasoreactivity.…”

Section: Discussionmentioning

confidence: 98%

Selective Endothelin‐A Receptor Blockade Attenuates Endotoxin‐Induced Pulmonary Hypertension and Pulmonary vascular dysfunction

et al. 2014

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Endothelin-1 is a potent mediator of sepsis-induced pulmonary hypertension (PH). The pulmonary vascular effects of selective blockade of endothelin receptor subtype A (ET A R) during endotoxemia remain unknown. We hypothesized that selective ET A R antagonism attenuates endotoxin-induced PH and improves pulmonary artery (PA) vasoreactivity. Adult male Sprague-Dawley rats (250-450 g) received lipopolysaccharide (LPS; Salmonella typhimurium; 20 mg/kg intraperitoneally) or vehicle 6 hours before hemodynamic assessment and tissue harvest. The selective ET A R antagonist sitaxsentan (10 or 20 mg/kg) or vehicle was injected intravenously 3 hours after receipt of LPS. Right ventricular systolic pressure, mean arterial pressure (MAP), cardiac output (CO), oxygenation (P/F ratio), and serum bicarbonate were measured. Bronchoalveolar lavage (BAL) cell differential and lung wet-to-dry ratios were obtained. Endothelium-dependent and endothelium-independent vasorelaxations were determined in isolated PA rings. PA interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) were measured. LPS caused PH, decreased MAP, CO, and serum bicarbonate, and increased PA IL-1β, IL-6, TNF-α, and iNOS mRNA. Sitaxsentan attenuated sepsis-induced PH and increased MAP. The P/F ratio, CO, serum bicarbonate, and BAL neutrophilia were not affected by sitaxsentan. In isolated PA rings, while not affecting phenylephrine-induced vasocontraction or endothelium-dependent relaxation, sitaxsentan dosedependently attenuated LPS-induced alterations in endothelium-independent relaxation. PA cytokine mRNA levels were not significantly attenuated by ET A R blockade. We conclude that ET A R blockade attenuates endotoxin-induced alterations in systemic and PA pressures without negatively affecting oxygenation. This protective effect appears to be mediated not by attenuation of sepsis-induced cardiac dysfunction, acidosis, or alveolar inflammation but rather by improved endothelium-independent vasorelaxation.

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Acute haemodynamic effects of cromakalim in patients with angina pectoris.

Cited by 23 publications

References 9 publications

Characterization of the vasodilatory action of testosterone in the human pulmonary circulation

Characterization of the vasodilatory action of testosterone in the human pulmonary circulation

Clinical Pharmacology of Potassium Channel Openers

Selective Endothelin‐A Receptor Blockade Attenuates Endotoxin‐Induced Pulmonary Hypertension and Pulmonary vascular dysfunction

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