Department of Physiology, Queen's University, Kingston, Ontario, Canada.
J Neuroendocrinol. 2012 Mar;24(3):504-10. doi: 10.1111/j.1365-2826.2011.02257.x.
The subfornical organ (SFO), a sensory circumventricular organ lacking the normal blood-brain barrier with well documented roles in cardiovascular regulation, has recently been identified as a potential site at which the adipokine, leptin, may act to influence central autonomic pathways. Systemic and central leptin administration has been shown to increase blood pressure and it has been suggested that selective leptin resistance contributes to obesity-related hypertension. Given the relationship between obesity and hypertension, the present study aimed to investigate the cardiovascular consequences of the direct administration of leptin into the SFO of young lean rats and in the diet-induced obesity (DIO) rat model, which has been shown to be leptin-resistant. Leptin administration (500 fmol) directly into the SFO of young rats resulted in rapid decreases in blood pressure (BP) [mean area under the curve (AUC) = -677.8 ± 167.1 mmHgs; n = 9], without an effect on heart rate (mean AUC = -21.2 ± 13.4 beats; n = 9), and these effects were found to be dose-related as microinjection of 5 pmol of leptin into the SFO had a larger effect on BP (mean AUC = -972.3 ± 280.1 mmHgs; n = 4). These BP effects were also shown to be site-specific as microinjection of leptin into non-SFO regions or into the ventricle was without effect on BP (non-SFO: mean AUC = -22.4 ± 55.3 mmHgs; n = 4; ventricle: mean AUC = 194.0 ± 173.0 mmHgs; n = 6). By contrast, microinjection of leptin into leptin-resistant DIO rats was without effect on BP (mean AUC = 205.2 ± 75.1 mmHg*s; n = 4). These observations suggest that the SFO may be an important relay centre through which leptin, in normal weight, leptin responsive rats, acts to maintain BP within normal physiological limits through descending autonomic pathways involved in cardiovascular control and that, in obese, leptin-resistant, rats leptin no longer influences SFO neurones, resulting in an elevated BP, thus contributing to obesity-related hypertension.
神经内分泌器官下丘室（SFO）是一种感觉性的脑-血屏障缺失的腔室器官，它在心血管调节方面有着很好的作用，最近被认为是一种潜在的位置，瘦素这种脂肪细胞因子可能作用于影响中枢自主神经通路。全身和中枢性给予瘦素已被证明可增加血压，并且有人提出选择性瘦素抵抗有助于肥胖相关的高血压。鉴于肥胖与高血压之间的关系，本研究旨在研究直接将瘦素注入年轻瘦大鼠的 SFO 以及饮食诱导肥胖（DIO）大鼠模型中的心血管后果，因为后者被证明是瘦素抵抗的。将瘦素（500fmol）直接注入年轻大鼠的 SFO 会导致血压迅速下降（平均 AUC = -677.8 ± 167.1mmHgs；n = 9），而对心率没有影响（平均 AUC = -21.2 ± 13.4 次；n = 9），并且这些作用呈剂量依赖性，因为将 5pmol 的瘦素注入 SFO 对血压的影响更大（平均 AUC = -972.3 ± 280.1mmHgs；n = 4）。这些血压作用也被证明是特异性的，因为将瘦素注入非 SFO 区域或脑室对血压没有影响（非 SFO：平均 AUC = -22.4 ± 55.3mmHgs；n = 4；脑室：平均 AUC = 194.0 ± 173.0mmHgs；n = 6）。相比之下，将瘦素注入瘦素抵抗的 DIO 大鼠中对血压没有影响（平均 AUC = 205.2 ± 75.1mmHg*s；n = 4）。这些观察结果表明，在正常体重、瘦素反应性大鼠中，SFO 可能是一个重要的中继中心，通过它，瘦素通过参与心血管控制的下行自主神经通路作用于维持血压在正常生理范围内，而在肥胖、瘦素抵抗的大鼠中，瘦素不再影响 SFO 神经元，导致血压升高，从而导致肥胖相关的高血压。
