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年轻成年肥胖 Zucker 高血压雌性大鼠的血糖控制和压力反射效率得到保持。

Preserved glycemic control and baroreflex efficacy in young adult hypertensive female obese Zucker rats.

机构信息

Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2021 Jul 1;321(1):R62-R78. doi: 10.1152/ajpregu.00341.2020. Epub 2021 May 12.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce6/8321785/2db13638cfa2/ajpregu.00341.2020_f001.jpg

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