Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Dec 2009
Atorvastatin restores the impaired vascular endothelium-dependent relaxations mediated by nitric oxide and endothelium-derived hyperpolarizing factors but not hypotension in sepsis.
Sepsis has been reported to impair endothelium-dependent vasodilations mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Although some studies demonstrate that statins can improve NO-mediated response in septic animals, little is known about its effect on the EDHF response. The present study examined the effects of atorvastatin pretreatment on sepsis-induced endothelial dysfunctions and hypotension in rats. ⋯ Sepsis abolished this response but atorvastatin restored it (22.55% +/- 2.50%). Atorvastatin, however, failed to prevent sepsis-induced hypotension. These results suggest that atorvastatin can restore impaired endothelium-dependent vasodilations mediated by NO and EDHF but not hypotension in sepsis.
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J. Cardiovasc. Pharmacol. · Oct 2009
Comparative StudyEffect of hydrogen sulfide in a porcine model of myocardial ischemia-reperfusion: comparison of different administration regimens and characterization of the cellular mechanisms of protection.
We investigate the impact of different regimens of parenteral hydrogen sulfide (H2S) administration on myocardium during ischemia-reperfusion (IR) and the molecular pathways involved in its cytoprotective effects. ⋯ This study demonstrates that infusion of H2S is superior to a bolus alone in reducing myocardial necrosis after IR injury, even though some markers of apoptosis and autophagy were affected in both H2S-treated groups. Thus, the current results indicate that infusion of H2S throughout IR may offer better myocardial protection from IR injury.
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J. Cardiovasc. Pharmacol. · Aug 2009
Randomized Controlled TrialDo proton pump inhibitors attenuate the effect of aspirin on platelet aggregation? A randomized crossover study.
It is common practice to coadminister proton pump inhibitors with aspirin to diminish the risk of upper gastrointestinal bleeding. This is the first study that investigated the potential impact of a proton pump inhibitor on aspirin effects on platelet aggregation. Twenty-four hypertensive subjects eligible for treatment with low-dose enteric-coated aspirin (LDECA) for primary prevention of cardiovascular disease were randomized to receive 100 mg LDECA or 100 mg LDECA plus 30 mg lansoprazole for 4 weeks. ⋯ A significant increase in salicylic levels was observed in patients on LDECA as well as in those on LDECA plus lansoprazole, whereas gastrin and pepsinogen I levels were increased only when lansoprazole was added. These data suggest that the concomitant use of the lansoprazole at 30-mg daily does not influence the long-term effect of LDECA on platelet aggregation. Furthermore, they might imply that an interaction of LDECA with other proton pump inhibitors on platelet aggregation is unlikely.
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J. Cardiovasc. Pharmacol. · Jun 2009
Cardiomyocyte S1P1 receptor-mediated extracellular signal-related kinase signaling and desensitization.
We examined the ability of sphingosine-1-phosphate (S1P) to desensitize extracellular signal-related kinase (ERK), a mitogen-activated protein kinase linked to antiapoptotic responses in the heart. In isolated adult mouse cardiomyocytes, S1P (10 nM-5 microM) induced ERK phosphorylation in a time- and dose-dependent manner. S1P stimulation of ERK was completely inhibited by an S1P1/3 subtype receptor antagonist (VPC23019), by a Gi protein inhibitor (pertussis toxin) and by a mitogen-activated protein kinase/ERK kinase inhibitor (PD98059). ⋯ This enhanced survival was abrogated by pretreatment with PD98059, VPC23019, or pertussis toxin. Thus, exogenous S1P induces rapid and reversible S1P1-mediated ERK phosphorylation. S1P-induced adult mouse cardiomyocyte survival requires ERK activation mediated via an S1P1-Gi pathway.
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J. Cardiovasc. Pharmacol. · May 2009
Metformin prevents myocardial reperfusion injury by activating the adenosine receptor.
Metformin improves cardiovascular outcomes in patients with type 2 diabetes compared with other glucose-lowering drugs. Experimental studies have shown that metformin can increase the intracellular concentration of adenosine monophosphate, which is a major determinant of the intracellular formation of adenosine. We hypothesize that metformin, given at reperfusion, can limit myocardial infarct size due to increased adenosine receptor stimulation. ⋯ Perfusion with metformin (50 microM) for the first 15 minutes of reperfusion reduced infarct size (percent area at risk) from 42% +/- 2% to 19% +/- 4% (n >or= 6; P < 0.01), which was blocked by a concomitant perfusion with the adenosine receptor antagonist 8-p-sulfophenyltheophylline (100 microM; 43% +/- 3%) or nitrobenzylthioinosine (a blocker of transmembranous adenosine transport; 1 microM; 45% +/- 5%). In addition, intravenous administration of metformin (5 mg/kg) reduced infarct size in a rat in situ model of myocardial infarction (34% +/- 6% vs. 62% +/- 5%; P < 0.01), which was completely abolished by 8-p-sulfophenyltheophylline (61% +/- 3%). We conclude that metformin, given at reperfusion, reduces infarct size in a rat model of myocardial infarction, which is critically dependent on adenosine receptor stimulation, probably via increased intracellular formation of adenosine.