Edison Biotechnology Institute (A.J., C.M.B., D.S., X.L., E.O.L., L.A.H., D.E.B., J.J.K.) Ohio University, Athens, Ohio 45701; Department of Biomedical Sciences (A.J., D.E.B., J.J.K.) and Department of Specialty Medicine (E.O.L.), Heritage College of Osteopathic Medicine, Athens, Ohio 45701; School of Applied Health Sciences and Wellness (C.M.B., X.L., D.E.B.) College of Health Sciences and Professions, Ohio University, Athens, Ohio 45701; and Department of Biological Sciences (A.J., J.J.K.) and Department of Social and Public Health (D.S.), Ohio University, Athens, Ohio 45701.
Endocrinology. 2014 Mar;155(3):975-86. doi: 10.1210/en.2013-1899. Epub 2013 Jan 1.
Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3-12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems.
肢端肥大症与心血管疾病的发病率增加有关。先前曾使用表达牛生长激素（bGH）基因的转基因小鼠来研究慢性 GH 刺激对心血管功能的影响。关于 bGH 小鼠收缩压（SBP）的结果存在矛盾。我们假设这些差异可能是由于先前研究中使用的小鼠年龄不同所致。在当前的研究中，从 3 到 12 个月大的雄性 bGH 小鼠每月评估一次 SBP。在此期间评估了已知会改变血压的因素，包括：脑利钠肽（BNP）和葡萄糖稳态标志物的水平，以及肾血管紧张素转换酶 2 和内皮型一氧化氮合酶的水平。从 6 个月大开始，与野生型对照相比，bGH 的 SBP 升高，并持续升高至 12 个月大。尽管 bGH 小鼠的血压和心脏 BNP mRNA 升高，但循环 BNP 水平降低。此外，bGH 小鼠的胰岛素水平随年龄呈下降趋势。例如，它们在 3 个月时出现高胰岛素血症，但到 11 个月时与野生型对照相比出现低胰岛素血症。这种胰岛素的减少伴随着 11 个月时葡萄糖耐量的改善。最后，11 个月大的 bGH 小鼠肾脏中的血管紧张素转换酶 2 和内皮型一氧化氮合酶表达严重降低。这些结果表明，bGH 小鼠的 SBP 升高依赖于年龄，与胰岛素抵抗无关，与利钠肽和肾素-血管紧张素系统的改变有关。
