Manaaki Manawa - The Centre for Heart Research, Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS, USA.
J Physiol. 2024 Aug;602(16):3909-3927. doi: 10.1113/JP286627. Epub 2024 Jul 29.
Type 2 diabetes (T2D) is often accompanied by hypertension, exaggerated blood pressure (BP) responses to sympatho-excitatory stressors, and raised cardiovascular disease risk. Appropriate respiratory-sympathetic coupling and sympathetic transduction to BP are important for short- and longer-term BP control. We tested the hypotheses that respiratory modulation of muscle sympathetic nerve activity (MSNA) and its transduction to BP would be impaired in T2D and associated with higher BP and respiratory-coupled BP variability. Resting MSNA, respiration and beat-to-beat BP were recorded in 20 T2D (49.1 ± 7.4 years; mean ± SD) and 13 healthy control (46.3 ± 9.4 years) participants. MSNA and the transduction of sympathetic bursts (signal-averaging) to mean arterial pressure (MAP) were compared at low and high lung volume phases. The peak MAP response following a sympathetic burst was lower during the high lung volume than low lung volume phase in controls (P = 0.005), whereas it was unchanged with phase in T2D participants (P = 0.522). Respiratory modulation of MSNA was impaired in T2D participants, who had an attenuated reduction in burst incidence from low to the high lung volume phase, versus controls (27.8 ± 38.4% vs. 49.4 ± 24.6%, respectively; P = 0.043). The T2D participants were grouped into unimpaired respiratory modulators (burst incidence modulation median or above) or impaired respiratory modulators (below median). Impaired modulators had higher systolic BP (133 ± 14 vs. 121 ± 11 mmHg, P = 0.046), greater Traube-Hering wave amplitudes (6.3 ± 2.4 vs. 4.6 ± 1.1 mmHg; P = 0.028) and higher BP variability (MAP average real variability, 2.0 ± 0.7 vs. 1.4 ± 0.3, P = 0.033). Respiratory modulation of MSNA and sympathetic transduction to BP are altered in T2D patients and may contribute to their increased hypertension and cardiovascular risk. KEY POINTS: Respiratory-sympathetic coupling and sympathetic transduction to blood pressure (BP) contribute to short- and longer-term BP control. Our understanding of these processes in health and type 2 diabetes (T2D), a condition with high prevalence of hypertension and cardiovascular risk, is incomplete. We found that respiration and sympathetic transduction to BP are coupled in healthy individuals. The mean arterial pressure response to a sympathetic burst was reduced during the high lung volume compared to the low lung volume phase. This coupling was absent in T2D. Respiratory modulation of muscle sympathetic nerve activity (MSNA) is impaired in T2D, with a blunted reduction of MSNA observed during the high lung volume phase. T2D patients with impaired respiratory MSNA modulation had augmented systolic BP, respiratory-related BP excursions (Traube-Hering waves) and BP variability. Abnormal respiratory modulation of MSNA and sympathetic transduction to BP in T2D may contribute to altered blood pressure control and cardiovascular risk in this population.
2 型糖尿病（T2D）常伴有高血压，对交感兴奋应激的血压反应增强，心血管疾病风险增加。适当的呼吸-交感耦合和交感神经对血压的传递对于短期和长期的血压控制非常重要。我们假设 T2D 患者的肌肉交感神经活动（MSNA）的呼吸调节及其对血压的传递会受损，并且与更高的血压和呼吸相关的血压变异性有关。在 20 名 T2D（49.1±7.4 岁；平均值±标准差）和 13 名健康对照者（46.3±9.4 岁）中记录了静息 MSNA、呼吸和每搏血压。在低肺容量和高肺容量阶段比较了 MSNA 和交感爆发（信号平均）对平均动脉压（MAP）的传递。在对照组中，MAP 的高峰反应在高肺容量阶段低于低肺容量阶段（P=0.005），而在 T2D 患者中，相位没有变化（P=0.522）。T2D 患者的 MSNA 呼吸调节受损，与对照组相比，他们在从低肺容量到高肺容量阶段时，爆发发生率的降低幅度较小（分别为 27.8±38.4%和 49.4±24.6%；P=0.043）。T2D 患者被分为呼吸调节不受影响者（爆发发生率调节中位数或以上）或呼吸调节受损者（低于中位数）。呼吸调节受损者的收缩压较高（133±14 与 121±11mmHg，P=0.046），Traube-Hering 波幅度较大（6.3±2.4 与 4.6±1.1mmHg；P=0.028），血压变异性较高（MAP 平均真实变异性，2.0±0.7 与 1.4±0.3，P=0.033）。T2D 患者的 MSNA 呼吸调节和交感神经对血压的传递发生改变，可能导致其高血压和心血管风险增加。关键点：呼吸-交感耦合和交感神经对血压（BP）的传递有助于短期和长期的血压控制。我们对健康和 2 型糖尿病（T2D）中这些过程的理解并不完整，T2D 是一种高血压和心血管风险高发的疾病。我们发现健康个体的呼吸和交感神经对 BP 是耦合的。与低肺容量相比，MAP 对交感爆发的反应在高肺容量时降低。在 T2D 中，这种耦合不存在。T2D 患者的 MSNA 呼吸调节受损，在高肺容量阶段观察到 MSNA 明显减少。T2D 患者的呼吸调节受损的 MSNA 调制，其收缩压、呼吸相关的 BP 波动（Traube-Hering 波）和 BP 变异性增加。T2D 患者的 MSNA 和交感神经对 BP 的呼吸调节异常可能导致该人群的血压控制和心血管风险改变。
