Cyclooxygenase products contribute to the exaggerated exercise pressor reflex evoked by static muscle contraction in male UCD-type 2 diabetes mellitus rats.

Cyclooxygenase (COX) products of arachidonic acid metabolism, specifically prostaglandins, play a role in evoking and transmitting the exercise pressor reflex in health and disease. Individuals with type 2 diabetes mellitus (T2DM) have an exaggerated exercise pressor reflex; however, the mechanisms for this exaggerated reflex are not fully understood. We aimed to determine the role played by COX products in the exaggerated exercise pressor reflex in T2DM rats. The exercise pressor reflex was evoked by static muscle contraction in unanesthetized, decerebrate, male, adult UCD-T2DM (n=8) and healthy Sprague-Dawley (n=8) rats. Changes (∆) in peak mean arterial pressure (MAP) and heart rate (HR) during muscle contraction were compared before and after intra-arterial injection of indomethacin (1 mg/kg) into the contracting hindlimb. Data are presented as mean ± SD. Inhibition of COX activity attenuated the exaggerated peak MAP (Before: ∆32 ± 13 mmHg, After: ∆18 ± 8 mmHg; P=0.004) and blood pressor index (BPi) (Before: ∆683 ± 324 mmHg.s, After: ∆361 ± 222 mmHg.s; P=0.006), but not HR (Before: ∆23 ± 8 bpm, After ∆19 ± 10 bpm; P=0.452) responses to muscle contraction in T2DM rats. In healthy rats, COX activity inhibition did not affect MAP, HR or BPi responses to muscle contraction. Inhibition of COX activity significantly reduced local production of prostaglandin E2 in T2DM and healthy rats. We conclude that peripheral inhibition of COX activity attenuates the pressor response to muscle contraction in T2DM rats, suggesting that COX products partially contribute to the exaggerated exercise pressor reflex in those with T2DM.