Inhibiting Cyclooxygenase Activity Attenuates the Exaggerated Exercise Pressor Reflex in Male UCD-Type 2 Diabetes Mellitus Rats

Abstract

It is well established that prostaglandins, a product of cyclooxygenase (COX) enzymes contribute to evoking the exercise pressor reflex. Previous studies suggest that COX expression is upregulated in the peripheral nerves of those with type 2 diabetes (T2D), likely due to low grade inflammation associated with the disease. The purpose of this study was to determine if COX activity in the exercising skeletal muscle exaggerates the exercise pressor reflex in T2D. We hypothesized that inhibiting COX activity in the hindlimb would reduce the exaggerated pressor response to muscle contraction in T2D rats. To do this, we evoked the exercise pressor reflex by statically contracting the skeletal muscle for 30s in unanesthetized, decerebrate rats. Experiments were performed on male University of California Davis (UCD)-T2D (n=8; body weight: 526 ± 42g) and Sprague Dawley rats (n=3; body weight: 473 ± 10g). Changes (Δ) in peak mean arterial pressure (MAP) and heart rate (HR) responses to exercise were compared before and after locally injecting indomethacin (1 mg/kg in 0.2 mL of 100 mM sodium carbonate), a COX 1 and 2 inhibitor, or its vehicle (0.2 mL of 100 mM sodium carbonate) into the arterial supply of the ipsilateral (contracting) and contralateral (non-contracting) hindlimb. Data are presented as mean ± SD. We found that local injection of indomethacin into the contracting hindlimb reduced the exaggerated peak pressor (ΔMAP: 30 ± 14 mmHg to 18 ± 8 mmHg; P<0.01) but not cardioaccelerator (ΔHR: 21 ± 8 bpm to 19 ± 11 bpm; P=0.59) responses in T2D rats, but did not reduce these responses in healthy rats (ΔMAP 14 ± 3 mmHg to 14 ± 6 mmHg; P>0.99; ΔHR: 10 ± 5 bpm to 13 ± 7 bpm; P=0.67). Conversely, local injection of indomethacin into the non-contracting hindlimb (n=4), as well as injection of the vehicle in the contracting hindlimb (n=4), did not affect the pressor response to muscle contraction in T2D rats. Developed tensions during muscle contraction were similar for all comparisons. In summary, our findings suggest that COX activity contributes to the exaggerated pressor response to muscle contraction in T2D rats. This project was supported by NIH R01 HL144723. This project was supported by NIH R01 HL144723. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.