P2X receptor‐mediated muscle pressor reflex in myocardial infarction (MI).

Abstract

We have recently reported that the ATP sensitive P2X receptor-mediated muscle pressor reflex is augmented in rats with heart failure (HF). However, the underlying mechanisms for this greater response to stimulation of P2X in MI rats is poorly understood. Thus, in this study we examined: 1) responsiveness of the P2X receptor to α,β-me ATP in control and HF rats; and 2) expression of P2X in the DRG in control rats and rats with HF due to chronic MI. Eight to 14 weeks after coronary artery ligation, the severity of MI was determined by echocardiography. The P2X receptor agonist, α, β-me ATP (0.0625, 0.125, 0.25 and 0.5 mM) was injected into the arterial supply of the hindlimb muscle to evoke a pressor response in 13 decerebrated rats (4 controls, 5 small MI with infarcts between 10-35%, and 4 large MI with infarcts >35% of the LV). The P2X agonist increased blood pressure and the effect was significantly accentuated in large MI rats as compared with small MI and control rats. In a second study, immunocytochemistry was used to compare the immunoreactivity of the DRG P2X receptor (in large and small diameter fibers of afferent neurons) in 8 rats with MI and in 6 control rats. 21±10% of DRG neurons in control rats and 31±2% of DRG neurons in MI rats were immunostaining positive for the PX2 receptor (NS for comparison of control vs. MI). P2X sensitivity to α, β-me ATP is enhanced in HF. However, expression of P2X receptors on DRG neurons is not increased in HF. Supported by NIH R01 HL075533 (Li), R01 HL078866 (Li) and R01 HL060800 (Sinoway).