Muscle mechanoreflex and metaboreflex responses after myocardial infarction in rats. Journal   Circulation. Citation   Circulation. 110(19):3049-54 Publication date   2004 Nov 9 Authors   Li J Sinoway AN Gao Z Maile MD Pu M Sinoway LI Investigators   Jianhua Li Min Pu Lawrence I. Sinoway Grant agencies   National Heart, Lung, and Blood Institute Grants   NHLBI R01 HL060800 NHLBI R01 HL075533 Abstract   BACKGROUND: During exercise, the sympathetic nervous system is activated and blood pressure and heart rate increase. In heart failure (HF), the muscle metaboreceptor contribution to sympathetic outflow is attenuated and the mechanoreceptor contribution is accentuated. Previous studies suggest that (1) capsaicin stimulates muscle metabosensitive vanilloid receptor subtype 1 (VR1), inducing a neurally mediated pressor response, and (2) activation of ATP-sensitive P2X receptors enhances the pressor response seen when muscle mechanoreceptors are engaged by muscle stretch. Thus, we hypothesized that the pressor response to VR1 stimulation would be smaller and the sensitizing effects of P2X stimulation greater in rats with HF due to chronic myocardial infarction (MI) than in controls. METHODS AND RESULTS: Eight to 14 weeks after coronary ligation, rats with infarcts >35% had an increased left ventricular end-diastolic pressure and a marked increase in heart weight. Capsaicin injected into the arterial supply of the hindlimb increased blood pressure by 39% (baseline, 93.9+/-9.5 mm Hg) in control animals but only by 8% (baseline, 94.8+/-10.1 mm Hg) in rats with large MIs (P<0.05). P2X receptor stimulation by alpha,beta-methylene ATP enhanced the pressor response to muscle stretch by 42% in control animals and by 72% in rats with large MIs (P<0.05). CONCLUSIONS: Compared with control animals, cardiovascular responses to VR1 stimulation are blunted and P2X-mediated responses are augmented in rats with HF owing to large MIs.