α7 nicotinic receptors play a role in regulation of cardiac hemodynamics

The α7 nicotinic receptors (NR) have been confirmed in the heart but their role in cardiac functions has been contradictory. To address these contradictory findings, we analyzed cardiac functions in α7 NR knockout mice (α7−/−) in vivo and ex vivo in isolated hearts. A standard limb leads electrocardiogram was used, and the pressure curves were recorded in vivo, in Arteria carotis and in the left ventricle, or ex vivo, in the left ventricle of the spontaneously beating isolated hearts perfused following Langedorff's method. Experiments were performed under basic conditions, hypercholinergic conditions, and adrenergic stress. The relative expression levels of α and β NR subunits, muscarinic receptors, β1 adrenergic receptors, and acetylcholine life cycle markers were determined using RT‐qPCR. Our results revealed a prolonged QT interval in α7−/− mice. All in vivo hemodynamic parameters were preserved under all studied conditions. The only difference in ex vivo heart rate between genotypes was the loss of bradycardia in prolonged incubation of isoproterenol‐pretreated hearts with high doses of acetylcholine. In contrast, left ventricular systolic pressure was lower under basal conditions and showed a significantly higher increase during adrenergic stimulation. No changes in mRNA expression were observed. In conclusion, α7 NR has no major effect on heart rate, except when stressed hearts are exposed to a prolonged hypercholinergic state, suggesting a role in acetylcholine spillover control. In the absence of extracardiac regulatory mechanisms, left ventricular systolic impairment is revealed. Cardiac functions were studied in/ex vivo in alpha nicotinic receptor 7 knockout (α7−/−) and wild‐type mice. Mutants showed a prolonged QT interval in cardiograms. Heart rate was preserved except for a slight loss of bradycardia in α7−/−‐isolated hearts after prolonged exposure to high acetylcholine, suggesting α7 nicotinic receptors may control cholinergic overstimulation. Isolated α7−/− hearts showed decreased left ventricular systolic pressure possibly because of a lack of sensory feedback mechanisms and efferent sympathetic and parasympathetic modulation. Adrenergic stress caused a higher increase in left ventricular systolic pressure in α7−/− hearts while β1 adrenergic receptor expression was preserved, suggesting a role of α7 nicotinic receptor in fine‐tuning adrenergic effects on the heart.