Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Jul 2012
Suppression of vascular inflammation by kinin B1 receptor antagonism in a rat model of insulin resistance.
Kinin B1 receptor (B1R) intervenes in a positive feedback loop to amplify and perpetuate the vascular oxidative stress in glucose-fed rats, a model of insulin resistance. This study aims at determining whether B1R blockade could reverse vascular inflammation in this model. ⋯ Kinin B1R antagonism reversed the upregulation of its own receptor and several pro-inflammatory markers in the aorta of glucose-fed rats. These data provide the first evidence that B1R may contribute to the low-grade vascular inflammation in insulin resistance, an early event in the development of type-2 diabetes.
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J. Cardiovasc. Pharmacol. · Feb 2012
Eribis peptide 94 reduces infarct size in rat hearts via activation of centrally located μ opioid receptors.
Eribis peptide 94 (EP 94) is a novel enkephalin derivative that binds with high potency to μ and δ opioid receptors with less affinity for the κ opioid receptor. This compound has recently been shown to produce an acute reduction in myocardial infarct size in the anesthetized pig and rat partially via an endothelial nitric oxide synthase and KATP channel-dependent mechanism. EP 94 also was found to produce a chronic reduction in infarct size 24 hours postdrug administration via the upregulation of inducible nitric oxide synthase in rats. ⋯ To test this hypothesis, rats were pretreated with the nonselective opioid antagonist, naloxone hydrochloride, which penetrates the blood-brain barrier or naloxone methiodide, the quaternary salt of naloxone hydrochloride, which does not penetrate the blood-brain barrier before EP 94 administration. In support of a central nervous system site of action for EP 94, naloxone hydrochloride completely blocked its cardioprotective effect, whereas naloxone methiodide had no effect. These results suggest that EP 94 reduces infarct size (expressed as a percent of the area at risk) in the rat primarily via activation of central μ opioid receptors.
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J. Cardiovasc. Pharmacol. · Nov 2011
Salvianolic acid A demonstrates cardioprotective effects in rat hearts and cardiomyocytes after ischemia/reperfusion injury.
Salvianolic acid A (Sal A), the water-soluble component from the root of the Salvia miltiorrhiza plant, possesses antioxidant, antiproliferative, and antiplatelet properties. However, whether it plays a role in the protection against ischemia-reperfusion (I/R) injury in rat hearts has yet to be elucidated. In the present study, we tested cell viability, shortening amplitude, necrosis, apoptosis, and the expression levels of Akt, phosphorylated Akt, Bcl-2, Bax, and caspase-3 after 3-hour simulated ischemia and 2- or 6-hour simulated reperfusion in cardiomyocytes. ⋯ The results also showed that Sal A significantly increased phosphorylation of Akt and that this phosphorylation can be partially inhibited by phosphoinositide 3-kinase/Akt inhibitor. Furthermore, Sal A improved I/R-induced myocardial contractile function and reduced infarct size. In summary, our results showed that Sal A prevents I/R-induced myocardial damage by reducing necrosis and apoptosis in isolated rat hearts and cardiomyocytes.
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J. Cardiovasc. Pharmacol. · Oct 2011
ReviewLocal termination of 3'-5'-cyclic adenosine monophosphate signals: the role of A kinase anchoring protein-tethered phosphodiesterases.
A kinase anchoring proteins (AKAPs) belong to a family of functionally related proteins capable of binding protein kinase A (PKA) and tether it to relevant targets. In this way, AKAPs organize macromolecular complexes to segregate PKA activity and retain signal specificity. In the heart, AKAP-PKA interaction is central to the regulation of cardiac contractility. ⋯ They possess diverse catalytic properties and multiple regulatory mechanisms and control the duration and amplitude of the cAMP signal, including its propagation in space. AKAPs, together with PKA, can also assemble phosphodiesterases thereby providing a means to locally control cAMP dynamics at the level of single macromolecular complexes. This allows for the fine tuning of the cAMP response to the specific demands of the cell.
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J. Cardiovasc. Pharmacol. · Oct 2011
Comparative StudyCost-effectiveness of levosimendan in patients with acute heart failure.
Heart failure is a major public health problem because of its high prevalence and impact on mortality, morbidity, quality of life, and social costs. The aim of this analysis was to estimate the effects of the novel inodilator levosimendan versus standard inotropic therapy (ST) of dobutamine in acute heart failure. A study population of 292 patients with acute heart failure was derived from an observational registry of patients referred to our department. ⋯ Rehospitalization rates were lower in the levosimendan group at 6 months (1.44% vs. 2.3%; P < 0.05) and 12 months (7.6% vs. 14.3%; P < 0.05). Mortality rate at 1 month was 2.1% versus 6.9% in the levosimendan and ST groups, respectively (P < 0.05). The per-capita cost of treatment with levosimendan was €78.86 higher than that with ST during the first hospitalization but €280.22 lower when the rehospitalization rate was considered.