Cyclooxygenase products contribute to enhanced muscle reflex in heart failure

Abstract

In heart failure (HF), reflex sympathetic nerve responses to muscle contraction are exaggerated. The present experiment was designed to test the role played by cyclooxygenase products, which are produced within contracting skeletal muscle, in the enhanced muscle reflex of HF. HF was induced by myocardial infarction (MI) after the coronary artery ligation in rats. Echocardiography was performed to determine fractional shortening (FS), an index of the left ventricular function. In decerebrate rats, we examined renal sympathetic nerve activity (RSNA) during 1‐min intermittent (1‐ to 4‐s stimulation‐to‐relaxation) contraction of left triceps surae muscles. RSNA responded synchronously as tension was developed, and the response was significantly (P<0.05) enhanced in MI rats [+28±2 arbitrary unit (a.u.); n=12] with FS <30% compared to control animals (+16±3 a.u.; n=13) with FS > 40% at the same tension development. After intravenous administration of the cyclooxygenase inhibitor indomethacin (5 mg kg−1), the enhanced RSNA response to contraction was significantly reduced in the MI rats by 44% (+15±5 a.u.), but no significant change was found in the control animals (+12±2 a.u.). These data suggest that cyclooxygenase products within active muscle, such as prostaglandins, play a role in the enhanced muscle reflex in HF. Supported by NIH R01 R01 HL075533 & R01 HL078866 (Li) and R01 HL060800 (Sinoway).