Alterations of muscarinic acetylcholine receptors-2, 4 and α7-nicotinic acetylcholine receptor expression after ischaemia / reperfusion in the rat isolated heart.

ABSTRACT

1. Cardiac acetylcholine receptors are involved in the negative inotropic effect of the vagus and the protection of the stimulated vagal nerve against myocardial ischaemic injury. Acetylcholine receptors consist of five types of muscarinic acetylcholine receptors (M AChR) and several nicotinic acetylcholine receptors (nAChR). Notably, ischaemic heart disease is accompanied by substantial withdrawal of vagal activity. However, it is not entirely clear what the changes of M(2,4) AChR and α7-nAChR expression are after cardiac ischaemia/reperfusion (I/R) injury. 2. Cardiac functions were continuously recorded in Langendorff mode during 30 min of ischaemia and 60 min of reperfusion. Lactate dehydrogenase (LDH) leakage was measured. M(2,4) AChRs and α7-nAChR expression were measured by reverse transcription polymerase chain reaction and western blot. 3. In hearts exposed to I/R injury, left ventricular development pressure, heart rate and ± dP/dt decreased significantly compared with the controls. LDH leakage increased with respect to the controls during reperfusion. 4. In normal hearts, expression of M(2,4) AChR in the left ventricle were lower than in atria and the right ventricle, whereas expression of α7-nAChR was dramatically higher in the left ventricle and right ventricle than the atria. After reperfusion, the mRNA and protein expression of M(2) AChR increased notably in the left and right ventricle, and α7-nAChR was enhanced significantly in the left ventricle. M(4) AChR mRNA expression reduced notably after ischaemia and recovered to the control level after reperfusion in the atria, but the protein level did not change. 5. In conclusion, the increase in M(2) AChR and α7-nAChR after reperfusion might be the compensatory response to myocardial I/R injury, providing new information for treatment of myocardial I/R injury.