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Abstract

Type 2 diabetics (T2DM) have an abnormal cardiovascular response to exercise. The exercise pressor reflex, which is evoked by metabolic and mechanical stimuli arising from the contracting muscle, is a critical cardiovascular regulatory mechanism during exercise and is exaggerated in hypertension, heart failure, and peripheral artery disease. A recent study found that T2DM patients have an augmented metaboreflex. However, whether the mechanoreflex is also augmented in T2DM is not known. PURPOSE: The purpose of the study was to test whether the mechanoreflex is exaggerated in T2DM. Furthermore, we tested the contribution of mechano-gated Piezo 1 and 2 channels to the mechanoreflex in T2DM. METHODS: In unanaesthetized, decerebrated rats we stretched the Achilles tendon for 30 s and measured changes in mean arterial pressure (MAP) and heart rate (HR) in 12 mo old male T2DM rats (BW=546±26 g, glucose=549±28 mg/dl, HbA1c=12.82±0.18%) and healthy male controls (CTL: BW=453±22 g, glucose=229±31 mg/dl, HbA1c=4.6±0.1%). To test the contribution of Piezo channels, we injected GsMTx-4 (10 mg), a known antagonist of Piezo 1 and 2 channels, into the arterial supply of the hindlimb and repeated the stretch maneuver. RESULTS: We found that the pressor (T2DM: ΔMAP=69±6 mmHg, n=5; CTL: ΔMAP=13±2 mmHg, n=5) and cardioaccelerator (T2DM: ΔHR=28±4 bpm, n=5; CTL: ΔHR=5±3 bpm, n=5) responses to tendon stretch were significantly greater in T2DM rats compared to CTL; pCONCLUSION: We conclude that T2DM significantly exaggerates the pressor and cardioaccelerator response to mechanoreflex activation and that Piezo channels play a significant role in evoking the mechanoreflex in T2DM rats.

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