Role of the carotid body chemoreceptors in blood flow and blood pressure regulation in type 2 diabetes

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI--COLUMBIA AT REQUEST OF AUTHOR.] Patients with type 2 diabetes (T2D) are at increased risk for developing cardiovascular disease. The carotid body (CB) chemoreceptors have been implicated in the pathogenesis of cardiovascular disease. Common characteristics of T2D (e.g., elevated systemic insulin and glucose concentrations) may increase CB afferent activity, suggesting a role for the CB chemoreceptors in the pathophysiology of T2D. We hypothesized individuals with T2D would exhibit exaggerated CB chemosensitivity compared to healthy controls. We further hypothesized the contribution of the CB chemoreceptors to heart rate (HR), forearm blood flow (FBF) and blood pressure (BP) at rest and in response to exercise would be greater in individuals with T2D compared to healthy controls. METHODS: Ten individuals with diagnosed T2D or an elevated fasting glucose less than 100 mg/dL (T2D/EFG, 5 male (M)/5 female (F), 53[plus or minus]2 yrs, 32[plus or minus]2 kg/m2) and ten healthy controls (3M/7F, 52[plus or minus]4 yrs, 25[plus or minus]1 kg/m2) participated. Minute ventilation (pneumotachography) was measured during short bouts of 5 percent oxygen (70-100 percent SpO2) to determine CB chemosensitivity (hypoxic ventilatory response). HR (ECG), BP (finger photoplethysmography), and FBF (Doppler ultrasound) were continuously measured across three trials: 1) 5 min normoxic rest followed by 3 min exposure to hyperoxia (100 percent oxygen), 2) 2 min isometric handgrip exercise (30 percent maximal voluntary contraction, MVC) followed by 3 min post-exercise circulatory occlusion (PECO), 3) 2 min isometric handgrip exercise (30 percent MVC) followed by PECO plus hyperoxia. RESULTS: CB chemosensitivity was greater in T2D/EFG (-1.26[plus or minus]0.16 L/min/percent SpO2) compared to controls (-0.57[plus or minus]0.11 L/min/percent SpO2, p less than 0.01). Suppression of the CB chemoreceptors with acute hyperoxia decreased basal HR (p less than 0.01) and tended to decrease mean BP (p=0.09), with no effect on FBF (p=0.34). Suppression of the CB chemoreceptors with acute hyperoxia during PECO decreased HR (p less than 0.05) and had no effect on mean BP or FBF (p greater than 0.05). The effect of hyperoxia on resting and PECO hemodynamics did not differ between T2D/EFG and controls (p greater than 0.05). CONCLUSION: Individuals with T2D and/or EFG exhibit exaggerated CB chemosensitivity to hypoxia. However, the contribution of the CB chemoreceptors to resting and PECO hemodynamics (HR, BP, FBF) does not differ between T2D/EFG and age-matched controls. Together, these data suggest CB sensitivity, but not activity or reactivity is exaggerated in T2D compared to control.