Department of Physiology, Second Military Medical University, Shanghai, China.
Acta Pharmacol Sin. 2009 Dec;30(12):1594-600. doi: 10.1038/aps.2009.165.
To determine the effects of the centrally antihypertensive drug moxonidine injected into the rostral ventrolateral medulla (RVLM) on baroreflex function in spontaneously hypertensive rats (SHR).
Baroreflex sensitivity control of renal sympathetic nerve activity (RSNA) and barosensitivity of the RVLM presympathetic neurons were determined following application of different doses of moxonidine within the RVLM.
Three doses (0.05, 0.5, and 5 nmol in 50 nL) of moxonidine injected bilaterally into the RVLM dose-dependently reduced the baseline blood pressure (BP) and RSNA in SHR. At the highest dose (5 nmol) of moxonidine injection, the maximum gain (1.24%+/-0.04%/mmHg) of baroreflex control of RSNA was significantly decreased. However, the lower doses (0.05 and 0.5 nmol) of moxonidine injection into the RVLM significantly enhanced the baroreflex gain (2.34%+/-0.08% and 2.01%+/-0.07%/mmHg). The moxonidine-induced enhancement in baroreflex function was completely prevented by the imidazoline receptor antagonist efaroxan but not by the alpha(2)-adrenoceptor antagonist yohimbine. A total of 48 presympathetic neurons were recorded extracellularly in the RVLM of SHR. Iontophoresis of applied moxonidine (30-60 nA) dose-dependently decreased the discharge of RVLM presympathetic neurons but also significantly increased the barosensitivity of RVLM presympathetic neurons.
These data demonstrate that a low dose of moxonidine within the RVLM has a beneficial effect on improving the baroreflex function in SHR via an imidazoline receptor-dependent mechanism.
确定在延髓头端腹外侧区(RVLM)注射中枢性降压药莫索尼定对自发性高血压大鼠(SHR)压力反射功能的影响。
在 RVLM 内给予不同剂量的莫索尼定,观察肾交感神经活性(RSNA)的压力反射敏感性和 RVLM 节前神经元的压力敏感性的变化。
双侧 RVLM 注射 0.05、0.5 和 5 nmol(50 nL)三种剂量的莫索尼定,可剂量依赖性地降低 SHR 的基础血压(BP)和 RSNA。在最高剂量(5 nmol)的莫索尼定注射时,RSNA 对压力反射的最大增益(1.24%+/-0.04%/mmHg)显著降低。然而,RVLM 内注射较低剂量(0.05 和 0.5 nmol)的莫索尼定可显著增强压力反射增益(2.34%+/-0.08%和 2.01%+/-0.07%/mmHg)。咪唑啉受体拮抗剂依福地平完全阻止了莫索尼定诱导的压力反射功能增强,但 α2-肾上腺素受体拮抗剂育亨宾则没有。共记录了 SHR 的 RVLM 中 48 个节前神经元。在 RVLM 中给予莫索尼定(30-60 nA)的电离子电泳,可剂量依赖性地降低 RVLM 节前神经元的放电,但也显著增加了 RVLM 节前神经元的压力敏感性。
这些数据表明,RVLM 内的低剂量莫索尼定通过咪唑啉受体依赖的机制,对改善 SHR 的压力反射功能具有有益作用。