Burke Sandra L, Barzel Benjamin, Jackson Kristy L, Gueguen Cindy, Young Morag J, Head Geoffrey A
Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Cardiovascular Endocrinology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Front Physiol. 2021 Mar 8;12:640373. doi: 10.3389/fphys.2021.640373. eCollection 2021.
The hypothalamic paraventricular nucleus (PVN) is an important site where an interaction between circulating angiotensin (Ang) and mineralocorticoid receptor (MR) activity may modify sympathetic nerve activity (SNA) to influence long-term elevation of blood pressure. We examined in conscious Ang II-treated rabbits, the effects on blood pressure and tonic and reflex renal SNA (RSNA) of microinjecting into the PVN either RU28318 to block MR, losartan to block Ang (AT) receptors or muscimol to inhibit GABA receptor agonist actions. Male rabbits received a moderate dose of Ang II (24 ng/kg/min subcutaneously) for 3 months ( = 13) or sham treatment ( = 13). At 3 months, blood pressure increased by +19% in the Ang II group compared to 10% in the sham ( = 0.022) but RSNA was similar. RU28318 lowered blood pressure in both Ang II and shams but had a greater effect on RSNA and heart rate in the Ang II-treated group ( < 0.05). Losartan also lowered RSNA, while muscimol produced sympatho-excitation in both groups. In Ang II-treated rabbits, RU28318 attenuated the blood pressure increase following chemoreceptor stimulation but did not affect responses to air jet stress. In contrast losartan and muscimol reduced blood pressure and RSNA responses to both hypoxia and air jet. While neither RU28318 nor losartan changed the RSNA baroreflex, RU28318 augmented the range of the heart rate baroreflex by 10% in Ang II-treated rabbits. Muscimol, however, augmented the RSNA baroreflex by 11% in sham animals and none of the treatments altered baroreflex sensitivity. In conclusion, 3 months of moderate Ang II treatment promotes activation of reflex RSNA principally via MR activation in the PVN, rather than via activation of AT receptors. However, the onset of hypertension is independent of both. Interestingly, the sympatho-excitatory effects of muscimol in both groups suggest that overall, the PVN regulates a tonic sympatho-inhibitory influence on blood pressure control.
下丘脑室旁核（PVN）是一个重要部位，循环中的血管紧张素（Ang）与盐皮质激素受体（MR）活性之间的相互作用可能会改变交感神经活动（SNA），从而影响血压的长期升高。我们在清醒的经血管紧张素II（Ang II）处理的兔子中进行了研究，向PVN微量注射RU28318以阻断MR、氯沙坦以阻断Ang（AT）受体或蝇蕈醇以抑制GABA受体激动剂作用，观察其对血压以及紧张性和反射性肾交感神经活动（RSNA）的影响。雄性兔子接受中等剂量的Ang II（24 ng/kg/min皮下注射）3个月（n = 13）或假处理（n = 13）。3个月时，Ang II组血压升高了19%，而假处理组升高了10%（P = 0.022），但RSNA相似。RU28318使Ang II组和假处理组的血压均降低，但对Ang II处理组的RSNA和心率影响更大（P < 0.05）。氯沙坦也降低了RSNA，而蝇蕈醇在两组中均产生交感兴奋作用。在Ang II处理的兔子中，RU28318减弱了化学感受器刺激后的血压升高，但不影响对喷气应激的反应。相比之下，氯沙坦和蝇蕈醇降低了对低氧和喷气应激的血压及RSNA反应。虽然RU28318和氯沙坦均未改变RSNA压力反射，但RU28318使Ang II处理的兔子心率压力反射范围扩大了10%。然而，蝇蕈醇使假处理动物的RSNA压力反射增强了11%，且所有处理均未改变压力反射敏感性。总之，3个月的中等剂量Ang II处理主要通过激活PVN中的MR而非激活AT受体来促进反射性RSNA的激活。然而，高血压的发生与两者均无关。有趣的是，蝇蕈醇在两组中的交感兴奋作用表明，总体而言，PVN对血压控制调节着一种紧张性交感抑制影响。
