Decreased myocardial injury and improved contractility after administration of a peptide derived against the alpha-interacting domain of the L-type calcium channel.
Bottom Line: Activation of the channel also alters mitochondrial function.In search of the mechanism for the effect, we found that intracellular calcium ([Ca(2+)]i, Fura-2), superoxide production (dihydroethidium fluorescence), mitochondrial membrane potential (Ψm, JC-1 fluorescence), reduced nicotinamide adenine dinucleotide production, and flavoprotein oxidation (autofluorescence) are decreased after application of AID-TAT peptide.Application of AID-TAT peptide significantly decreased infarct size and supported contractility up to 12 weeks postcoronary artery occlusion as a result of a decrease in metabolic demand during reperfusion.
Affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA, Australia (H.M.V., L.C.H.).Show MeSH
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Mentions: Rats underwent coronary artery ligation, and within 5 minutes after commencement of reperfusion, 1 or 10 μmol/L of AID‐TAT peptide or AID(S)‐TAT peptide was injected into the LV. The chest was closed, and rats were allowed to recover for up to 12 weeks. In a group of rats, saline was injected instead of peptide (“saline”), and in another group of rats, the chest was opened and closed without undergoing cardiac surgery and rats were allowed to recover (“sham”). Before sacrifice, ventricular function (LVPs and ±dP/dT) was assessed after catheterization of the LV. At the time of sacrifice, hearts were excised and weighed and infarct size was assessed. Consistent with our ex vivo data, rats treated with 1 or 10 μmol/L of AID‐TAT peptide had significantly smaller infarcts than rats treated with AID(S)‐TAT peptide (Figure 8A and 8B). This was evident at 6 and 12 weeks after CAL (Figure 8B). At 12 weeks, heart/body weight ratios were larger in rats treated with AID(S)‐TAT, compared to rats treated with AID‐TAT peptide (Figure 8C). More important, left ventricle systolic pressure LVSP (Figure 8D) and max dP/dT (Figure 8E) were significantly improved at 12 weeks post‐CAL in rats treated with 10 μmol/L of AID‐TAT peptide. Because the AID‐TAT peptide also binds the smooth muscle isoform of ICa‐L, we tested whether the peptide acutely altered arterial blood pressure in rats. After dual catheterization of the femoral artery and LV, rats were injected intravenously with 1 μmol/L of AID‐TAT. Both the arterial and LV blood pressures were recorded over 30 minutes. After 30 minutes, 10 μmol/L of AID‐TAT was injected and both pressures were recorded for a further 60 minutes. No change in arterial pressure was observed in the rats (Figure 8F).
Affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA, Australia (H.M.V., L.C.H.).