Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke

Abstract: Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Int. J. Mol. Sci. 2013, 14 18900 Therefore, antihypertensive treatments are recommended for the prevention of stroke. Thre

Clinical Neuroprotective Drugs for Treatment and Prevention of Stroke

Abstract: Stroke is an enormous public health problem with an imperative need for more effective therapies. In therapies for ischemic stroke, tissue plasminogen activators, antiplatelet agents and anticoagulants are used mainly for their antithrombotic effects. However, free radical scavengers, minocycline and growth factors have shown neuroprotective effects in the treatment of stroke, while antihypertensive drugs, lipid-lowering drugs and hypoglycemic drugs have shown beneficial effects for the prevention of stroke. In the present review, we evaluate the treatment and prevention of stroke in light of clinical studies and discuss new anti-stroke effects other than the mai

www.mdpi.com/journal/ijms The Efficacy of Edaravone (Radicut), a Free Radical Scavenger, for Cardiovascular Disease

Abstract: Edaravone was originally developed as a potent free radical scavenger, and has been widely used to treat acute ischemic stroke in Japan since 2001. Free radicals play an important role in the pathogenesis of a variety of diseases, such as cardiovascular diseases and stroke. Therefore, free radicals may be targets for therapeutic intervention in these diseases. Edaravone shows protective effects on ischemic insults and inflammation in the heart, vessel, and brain in experimental studies. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic, and anti-cytokine effects in cardiovascular diseases and stroke. Edaravone has preventive effects on myocardial injury following ischemia and reperfusion in patients with acute myocardial infarction. Edaravone may represent a new therapeutic intervention for endothelial dysfunction in the setting of atherosclerosis, heart failure, diabetes, or hypertension, because these diseases result from oxidative stress and/or cytokine-induced apoptosis. This review evaluates the potential of edaravone for treatment of cardiovascular disease, and covers clinical and experimenta

Correction: Kikuchi, K., et al., Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke. Int. J. Mol. Sci. 2013, 14, 18899–18924.

The original version of the paper [1] reports that “This ACTIVE I study was supported by Pfizer” (Page 18905). However, the sponsors of the ACTIVE I study were actually Bristol-Myers Squibb and Sanofi-Aventis rather than Pfizer

Correction: Kikuchi, K., et al., Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke. Int. J. Mol. Sci. 2013, 14, 18899–18924.

The original version of the paper [1] reports that "This ACTIVE I study was supported by Pfizer" (Page 18905). However, the sponsors of the ACTIVE I study were actually Bristol-Myers Squibb and Sanofi-Aventis rather than Pfizer. [...

Acetylcholine modulation of high-voltage-activated calcium channels in the neurones acutely dissociated from rat paratracheal ganglia

1. The modulation of high-voltage-activated (HVA) Ca(2+) channels by acetylcholine (ACh) was studied in the paratracheal ganglion cells acutely dissociated from 2-week-old Wistar rats by use of the nystatin perforated patch recording configuration under voltage-clamp conditions. 2. ACh inhibited the HVA Ca(2+) currents in a concentration- and voltage-dependent manner. 3. The inhibition was mimicked by a muscarinic agonist, oxotremorine. Pirenzepine and methoctramine produced parallel shifts to the right in the ACh concentration-response curves. Schild analysis of the ACh concentration-ratios yield pA(2) values for pirenzepine and methoctramine of 6.85 and 8.57, respectively, suggesting the involvement of an M(2) receptor. 4. Nifedipine, ω-conotoxin-GVIA and ω-conotoxin-MVIIC reduced the HVA I(Ca) by 16.8, 59.2 and 6.3%, respectively. A current insensitive to all of these Ca(2+) antagonists, namely `R-type', was also observed. The results indicated the existence of L-, N-, P/Q-, and R-type Ca(2+) channels. 5. The ACh-sensitive current component was markedly reduced in the presence of ω-conotoxin-GVIA, but not with both nifedipine and ω-conotoxin-MVIIC. ACh also inhibited the R-type HVA I(Ca) remaining in saturating concentrations of nifedipine, ω-conotoxin-GVIA and ω-conotoxin-MVIIC. 6. The inhibitory effect of ACh was prevented by pretreatment with pertussis toxin. 7. It was concluded that ACh selectively reduces both the N- and R-type Ca(2+) channels, by activating pertussis toxin sensitive G-protein through the M(2) muscarinic receptor in paratracheal ganglion cells