Rahmouni K, Barthelmebs M, Grima M, Imbs J L, De Jong W
Institut de Pharmacologie, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Hypertension. 2001 Oct;38(4):902-6. doi: 10.1161/hy1001.091781.
We recently showed that brain mineralocorticoid receptors (MRs) are involved in blood pressure and kidney function control in normotensive Wistar rats. We now assessed the involvement of brain MRs in spontaneously hypertensive rats (SHR), in which the presence of adrenocorticoids has been shown to be required for the development of hypertension. The effect of a single intracerebroventricular (ICV) injection of an MR antagonist (RU28318) on systolic blood pressure (SBP) and renal function was examined in conscious adult SHR and Wistar-Kyoto rats (WKY) maintained on a standard-sodium diet (0.4% Na(+)). In WKY, a long-lasting decrease in SBP was caused by the ICV injection of 10 ng RU28318 as previously reported in Wistar rats, associated with increased urinary excretion of water and electrolytes. In SHR maintained on the standard diet, the ICV injection of RU28318 (10 or 100 ng) had no effect on cardiovascular and renal functions. However, the ICV injection of 10 ng RU28318 in SHR after 3 weeks of high sodium intake (8% Na(+)) caused a long-lasting decrease in SBP. The effect was present at 8 hours (DeltaSBP 34+/-2 mm Hg), persisted at 24 hours (DeltaSBP 29+/-1 mm Hg), and disappeared at 48 hours after the injection. The hypotension was not associated with changes in heart rate, urinary excretion of water and electrolytes, and plasma renin activity, whereas renal denervation did not affect the decrease in SBP. A more pronounced decrease in SBP (49+/-3 mm Hg at 8 hours) was observed with 100 ng RU28318. This dose of the antagonist was without effect after subcutaneous administration. Thus, brain MRs appear to participate in the maintenance of hypertension in conscious adult SHR sensitized by sodium loading.
我们最近发现，脑盐皮质激素受体（MRs）参与正常血压的Wistar大鼠的血压和肾功能调控。我们现在评估脑MRs在自发性高血压大鼠（SHR）中的作用，在SHR中，肾上腺皮质激素的存在已被证明是高血压发生所必需的。在以标准钠饮食（0.4% Na⁺）饲养的成年清醒SHR和Wistar - Kyoto大鼠（WKY）中，研究了单次脑室内（ICV）注射MR拮抗剂（RU28318）对收缩压（SBP）和肾功能的影响。在WKY中，如先前在Wistar大鼠中所报道的，ICV注射10 ng RU28318导致SBP长期下降，同时伴有水和电解质尿排泄增加。在以标准饮食饲养的SHR中，ICV注射RU28318（10或100 ng）对心血管和肾功能没有影响。然而，在高钠摄入（8% Na⁺）3周后的SHR中ICV注射10 ng RU28318导致SBP长期下降。该效应在注射后8小时出现（ΔSBP 34±2 mmHg），在24小时持续存在（ΔSBP 29±1 mmHg），并在48小时消失。低血压与心率、水和电解质尿排泄以及血浆肾素活性的变化无关，而肾去神经支配并不影响SBP的下降。注射100 ng RU28318观察到SBP有更明显的下降（8小时时为49±3 mmHg）。该剂量的拮抗剂皮下给药无效。因此，脑MRs似乎参与了经钠负荷致敏的成年清醒SHR高血压的维持。
