Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas.
Am J Physiol Regul Integr Comp Physiol. 2021 Jul 1;321(1):R62-R78. doi: 10.1152/ajpregu.00341.2020. Epub 2021 May 12.
Obese Zucker rats (OZRs) develop hypertension and hyperinsulinemia by 3 mo of age. Male OZRs also have diminished baroreflex-mediated activation of nucleus tractus solitarius (NTS) and bradycardia, which are improved by correcting their hyperglycemia. Conversely, 3-mo-old female OZRs and lean Zucker rats (LZRs) have equivalent baroreflex-mediated bradycardia that is impaired in 6-mo-old OZRs. We hypothesized that 3-mo-old female OZRs maintain NTS activation and baroreflexes coincident with glycemic control. We also hypothesized that 6-mo-old female OZRs develop impaired baroreflexes with hyperglycemia and diminished NTS activation. In 12- to 16-wk-old females, sympathetic nerve activity (SNA) and arterial pressure (AP) were higher in OZRs than LZRs. However, baroreflex-mediated inhibition of SNA and bradycardia were equivalent in female OZRs and LZRs. Unlike deficits in male OZRs, female OZRs and LZRs had no differences in phenylephrine-induced c-Fos expression in NTS or decreases in SNA and AP evoked by glutamate into NTS. Compared with hyperglycemia in male OZRs (217.9 ± 34.4 mg/dL), female OZRs had normal fed blood glucose levels (108.2 ± 1.6 mg/dL in LZRs and 113.6 ± 3.5 mg/dL in OZRs) with emerging glucose intolerance. Conscious 24- to 27-wk-old female OZRs had impaired baroreflex-mediated bradycardia, but fed blood glucose was modestly elevated (124.2 ± 5.2 mg/dL) and phenylephrine-induced c-Fos expression in NTS was comparable to LZRs. These data suggest that better glycemic control in 3-mo-old female OZRs prevents diminished NTS activation and baroreflexes, supporting the notion that hyperglycemia impairs these responses in male OZRs. However, 6-mo-old female OZRs had impaired baroreflex efficacy without diminished NTS activation or pronounced hyperglycemia, suggesting baroreflex deficits develop by different mechanisms in female and male OZRs.
肥胖型 Zucker 大鼠(OZRs)在 3 月龄时就会发展为高血压和高胰岛素血症。雄性 OZRs 的压力反射介导的孤束核(NTS)激活和心动过缓也会减弱,但通过纠正高血糖可以得到改善。相反,3 月龄的雌性 OZRs 和 lean Zucker 大鼠(LZRs)的压力反射介导的心动过缓相当,但 6 月龄的 OZRs 则会受损。我们假设 3 月龄的雌性 OZRs 通过血糖控制来维持 NTS 激活和压力反射。我们还假设,6 月龄的雌性 OZRs 会在高血糖的情况下出现压力反射受损和 NTS 激活减弱。在 12 至 16 周龄的雌性大鼠中,OZRs 的交感神经活动(SNA)和动脉压(AP)均高于 LZRs。然而,OZRs 和 LZRs 的压力反射介导的 SNA 抑制和心动过缓相当。与雄性 OZRs 的缺陷不同,雌性 OZRs 和 LZRs 的 NTS 中苯肾上腺素诱导的 c-Fos 表达或谷氨酸诱发的 NTS 中的 SNA 和 AP 下降没有差异。与雄性 OZRs 的高血糖(217.9 ± 34.4mg/dL)相比,雌性 OZRs 的空腹血糖水平正常(LZRs 为 108.2 ± 1.6mg/dL,OZRs 为 113.6 ± 3.5mg/dL),且出现葡萄糖耐量受损。清醒的 24 至 27 周龄的雌性 OZRs 的压力反射介导的心动过缓受损,但空腹血糖略有升高(124.2 ± 5.2mg/dL),NTS 中苯肾上腺素诱导的 c-Fos 表达与 LZRs 相当。这些数据表明,3 月龄的雌性 OZRs 更好的血糖控制可以防止 NTS 激活和压力反射减弱,这支持了高血糖会损害雄性 OZRs 这些反应的观点。然而,6 月龄的雌性 OZRs 的压力反射效能受损,而 NTS 激活或明显的高血糖没有减弱,这表明雌性和雄性 OZRs 的压力反射缺陷可能通过不同的机制发展。