Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Jan 2007
Clinical TrialRapid switch from intravenous epoprostenol to intravenous treprostinil in patients with pulmonary arterial hypertension.
Intravenous epoprostenol improves exercise capacity and survival in patients with pulmonary arterial hypertension (PAH); however, chemical instability and a short half-life have caused limitations in its use. The chemically stable prostacyclin analogue treprostinil has a longer half-life, and improves hemodynamics and signs/symptoms of PAH. This study investigated the feasibility of transitioning patients with PAH from intravenous epoprostenol to intravenous treprostinil using a rapid switch protocol. ⋯ At week 12, the mean treprostinil dose was 62 +/- 30 ng/kg/min. All patients reported less prostacyclin-related side effects with treprostinil and remained on treprostinil after study completion. Selected patients with PAH can be safely transitioned from intravenous epoprostenol to intravenous treprostinil using a rapid switch protocol.
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J. Cardiovasc. Pharmacol. · Nov 2006
The effect of flutamide on systemic and renal hemodynamics in Zucker diabetic rats: paradoxic renal vasodilator response to endothelin-1 and TXA2 receptor activation in female sex.
There is increasing evidence that endogenous sex hormones regulate vascular reactivity, and testosterone may contribute to the worse prognosis for renal disease in men. Male Zucker diabetic rats exhibit improved renal hemodynamic responses after castration. It is, however, unclear whether endogenous testosterone affects renal and systemic microcirculatory responses in the female sex, especially in type 2 diabetes. ⋯ Flutamide administration to FZDR resulted in the reversal of abnormal systemic and renal alpha-1-mediated vasoconstriction and enhanced nitric oxide-mediated vasodilation. Flutamide caused a paradoxic but specific increase in renal perfusion during ET-1 and TXA2 receptor activation, which could be renoprotective in females. The salutary effects of flutamide on vascular reactivity in the FZDR may be mediated by a protein kinase C-dependent mechanism. These results are compatible with the notion that endogenous testosterone may regulate systemic and renal microcirculation in the female sex and in the type 2 diabetic state.
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J. Cardiovasc. Pharmacol. · May 2006
Statins blunt thrombin-induced down-regulation of endothelial nitric oxide synthase expression in human endothelial cells.
Thrombin plays a pivotal role in the pathophysiology of acute coronary syndromes by mediating thrombus formation and endothelium-dependent vasomotor dysfunction. In human endothelial cells, prolonged incubation with thrombin down-regulates endothelial nitric oxide synthase (eNOS) expression via activation of Rho. Statins are effective in patients with acute coronary syndromes. ⋯ Simvastatin (10 micromol/L) and cerivastatin (10 micromol/L) significantly decreased thrombin-induced membrane translocation of Rho A. Therefore, statins blunt thrombin-induced down-regulation of eNOS expression in human endothelial cells. This finding provides a novel mechanism of the pleiotropic effects of statins, which may be beneficial for patients with acute coronary syndromes.
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J. Cardiovasc. Pharmacol. · May 2006
Nicorandil but not ISDN upregulates endothelial nitric oxide synthase expression, preventing left ventricular remodeling and degradation of cardiac function in Dahl salt-sensitive hypertensive rats with congestive heart failure.
Cardiac endothelial nitric oxide synthase (ecNOS) was suppressed and inducible NOS (iNOS) enhanced at the decompensated heart failure stage in 18-week-old Dahl salt-sensitive (DS) hypertensive rats to which a high-salt diet had been administered from the age of 6 weeks. Nicorandil (NIC) enhanced ecNOS by activating Adenosine triphosphate-sensitive potassium channels (K-ATP channels) in the normal rat left ventricle. In this study, left ventricular hypertrophy, remodeling, function, cardiac ecNOS, and iNOS were compared between NIC and isosorbide dinitrate (ISDN) treatments in DS hypertensive rats with congestive heart failure. ⋯ However, no intragroup differences in iNOS mRNA or protein levels were observed for the 3 groups. More significant improvements in cardiac function and LV hypertrophy regression were observed in an NIC group than in an ISDN group of DS hypertensive rats. Activation of the K-ATP channel seems to induce this beneficial effect, which may be mediated in part by enhanced ecNOS expression in the heart in DS hypertensive congestive heart failure rat model.
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J. Cardiovasc. Pharmacol. · Dec 2005
Duration of the beneficial effects of levosimendan in decompensated heart failure as measured by echocardiographic indices and B-type natriuretic peptide.
Levosimendan is effective in the treatment of decompensated heart failure. The beneficial effects of a single dose of levosimendan last much longer than those of other inotropes. However, the exact duration of the beneficial effects is unknown. ⋯ Plasma BNP also displayed the same pattern of transient improvements. In conclusion, LS transiently improved the cardiac function, and the effects lasted for at least 7 days after discontinuation of infusion. Most effects, except LVEF, were not significantly different from baseline on day 30.