α7-nAChRs-mediated therapeutic angiogenesis accounts for the advantageous effect of low nicotine doses against myocardial infarction in rats

Angiogenesis accelerates tissue regeneration in a variety of ischemic conditions including myocardial infarction (MI). Here we tested the hypothesis that angiogenesis induced by alpha 7-nicotinic acetylcholine receptors (alpha 7nAChRs) mitigates histopathological, electrocardiographic, and molecular consequences of MI in rats. These profiles were evaluated in the isoprenaline (85 mg/kg/day i. p. For 2 days) MI rat model treated with or without nicotine or PHA-543613 (PHA, selective alpha 7-nAChR agonist). Isoprenaline-insulted rats showed (i) ECG signs of MI such as significant ST-segment elevations and prolonged QT-intervals, (ii) deteriorated left ventricular histopathological scoring and elevated inflammatory cell infiltration, (iii) reduced immunohistochemical expression of cardiac CD34, a surrogate marker of capillary density, (iv) decreased cardiac expression of iNOS and alpha 7nAChRs, and (v) adaptive increases in cardiac HO-1 expression and plasma angiogenic markers such as vascular endothelial growth factor (VEGF) and nitric oxide (NO). These effects of isoprenaline, except cardiac iNOS and alpha 7-nAChRs downregulation, were ameliorated in rats treated with a low dose (20 mu g/kg/day s. c. For 16 days) of nicotine or PHA. We also show that concurrent alpha 7-nAChR blockade by methyllycaconitine (MLA, 40 mu g/kg/day, for 16 days) reversed the ECG, histopathological, and capillary density effects of nicotine, thereby reinforcing the advantageous cardioprotective and anti-ischemic roles of alpha 7-nAChRs in this setting. The observed results showed promising effects on isoprenaline induced myocardial damage. In conclusion, the activation of alpha 7-nAChRs by doses of nicotine or PHA in the microgram scale promotes neovascularization and offers a promising therapeutic strategy for MI. Category: Cardiovascular Pharmacology.

Automated summary

α7-nicotinic acetylcholine receptor-induced angiogenesis alleviates pathological and electrocardiographic signs of myocardial infarction in rats, suggesting a promising therapeutic strategy for ischemic conditions.