Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Brain Res. 2012 Apr 4;1447:28-37. doi: 10.1016/j.brainres.2012.01.060. Epub 2012 Feb 1.
Several models of chronic sympathetic hyperactivity are associated with an increase in excitatory angiotensinergic and glutamatergic activity, and a decrease in GABAergic activity in the PVN. The present study evaluated whether activation of glutamate and AT1 receptors in the PVN contributes to the maintenance of resting BP in Dahl salt sensitive (S) rats on regular or high salt diet for 4-6 weeks. Candesartan and kynurenate were infused bilaterally into the PVN and BP and heart rate (HR) were recorded. Both candesartan and kynurenate in the PVN did not change MAP and HR in normotensive Dahl salt resistant (R) and S rats on regular salt diet or in R rats on high salt diet. In hypertensive Dahl S rats on high salt diet, candesartan decreased MAP (-14±2 mm Hg), and tended to increase HR (22±5 bpm). Kynurenate decreased both MAP (-22±3 mm Hg) and HR (-42±7 bpm) in these rats. At the peak BP decrease by candesartan, kynurenate in the PVN further decreased BP by ~50% (-14±2 mm Hg), whereas candesartan did not further decrease BP at the peak BP response to kynurenate (-4±2 mm Hg). These results indicate that activation of glutamate and AT1-receptors in the PVN contributes to the maintenance of BP in hypertensive Dahl S rats, but not normotensive Dahl S and R rats. The increased BP response to AT1-receptor activation in the PVN of hypertensive Dahl S appears to be mediated by enhanced local glutamate receptor activation, but another mechanism(s) appears to further enhance glutamate responses.
几种慢性交感神经活性亢进模型与 PVN 中兴奋性血管紧张素能和谷氨酸能活性增加以及 GABA 能活性降低有关。本研究评估了 PVN 中谷氨酸和 AT1 受体的激活是否有助于维持在常规或高盐饮食中 4-6 周的 Dahl 盐敏感（S）大鼠的静息血压。坎地沙坦和犬尿酸分别双侧输注到 PVN 中，并记录血压和心率（HR）。PVN 中的坎地沙坦和犬尿酸均未改变正常血压 Dahl 盐抵抗（R）和 S 大鼠在常规盐饮食或 R 大鼠在高盐饮食中的平均动脉压（MAP）和 HR。在高盐饮食的高血压 Dahl S 大鼠中，坎地沙坦降低 MAP（-14±2mmHg），并倾向于增加 HR（22±5bpm）。犬尿酸降低了这些大鼠的 MAP（-22±3mmHg）和 HR（-42±7bpm）。在坎地沙坦降低血压的峰值时，PVN 中的犬尿酸使血压进一步降低了约 50%（-14±2mmHg），而犬尿酸对坎地沙坦的峰值血压反应时，坎地沙坦并未进一步降低血压（-4±2mmHg）。这些结果表明，PVN 中谷氨酸和 AT1 受体的激活有助于维持高血压 Dahl S 大鼠的血压，但对正常血压的 Dahl S 和 R 大鼠则不然。在高血压 Dahl S 大鼠中，对 AT1 受体激活的血压反应增加似乎是通过增强局部谷氨酸受体激活介导的，但另一种机制似乎进一步增强了谷氨酸反应。
