Salo Lauren M, Nalivaiko Eugene, Anderson Colin R, McAllen Robin M
Howard Florey Institute, University of Melbourne, Victoria, Australia.
Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H318-24. doi: 10.1152/ajpheart.00951.2008. Epub 2008 Dec 12.
The sympathetic actions of medullary raphé neurons on heart rate (HR), atrioventricular conduction, ventricular contractility, and rate of relaxation were examined in nine urethane-anesthetized (1-1.5 g/kg iv), artificially ventilated rats that had been adrenalectomized and given atropine methylnitrate (1 mg/kg iv). Mean arterial pressure (MAP), ECG, and left ventricular pressure were recorded. The peak rates of rise and fall in the first derivative of left ventricular (LV) pressure (dP/dtmax and dP/dtmin, respectively) and the stimulus-R ($-R) interval were measured during brief periods of atrial pacing at 8.5 Hz before and after ventral medullary raphé neurons were activated by dl-homocysteic acid (DLH, 0.1 M) or inhibited by GABA (0.3 M) in local microinjections (90 nl). LV dP/dtmax values were corrected for the confounding effect of MAP, determined at the end of the experiments after giving propranolol (1 mg/kg iv) to block sympathetic actions on the heart. DLH microinjections into the ventral medullary raphé region increased HR by 44 +/- 2 beats/min, LV dP/dtmax by 1,055 +/- 156 mmHg/s, and the negative value of LV dP/dtmin by 729 +/- 204 mmHg/s (all, P < 0.001) while shortening the $-R interval by 2.8 +/- 0.8 ms (P < 0.01). GABA microinjections caused no significant change in HR, LV dP/dtmax, or $-R interval but reduced LV dP/dtmin from -5,974 +/- 93 to -5,548 +/- 171 mmHg/s and MAP from 115 +/- 4 to 105 +/- 5 mmHg (both, P < 0.01). Rises in tail skin temperature confirmed that GABA injections effectively inhibited raphé neurons. When activated, the neurons in the ventral medullary raphé region thus enhance atrioventricular conduction, ventricular contractility, and relaxation in parallel with HR, but they provide little or no tonic sympathetic drive to the heart.
在9只经乌拉坦麻醉(静脉注射1 - 1.5 g/kg)、人工通气、已切除肾上腺并给予硝酸甲基阿托品(静脉注射1 mg/kg)的大鼠中,研究了延髓中缝神经元对心率(HR)、房室传导、心室收缩力和舒张速率的交感神经作用。记录平均动脉压(MAP)、心电图(ECG)和左心室压力。在腹侧延髓中缝神经元被dl - 高半胱氨酸(DLH,0.1 M)激活或被γ - 氨基丁酸(GABA,0.3 M)局部微量注射(90 nl)抑制之前和之后,在8.5 Hz心房起搏的短时间内,测量左心室(LV)压力一阶导数的上升和下降峰值速率(分别为dP/dtmax和dP/dtmin)以及刺激 - R($ - R)间期。LV dP/dtmax值针对MAP的混杂效应进行了校正(在实验结束时给予普萘洛尔(静脉注射1 mg/kg)以阻断交感神经对心脏的作用后确定MAP)。向腹侧延髓中缝区域微量注射DLH使HR增加44±2次/分钟,LV dP/dtmax增加1,055±156 mmHg/s,LV dP/dtmin的负值增加729±204 mmHg/s(均为P < 0.001),同时使$ - R间期缩短2.8±0.8 ms(P < 0.01)。微量注射GABA对HR、LV dP/dtmax或$ - R间期无显著影响,但使LV dP/dtmin从 - 5,974±93降至 - 5,548±171 mmHg/s,MAP从115±4降至105±5 mmHg(均为P < 0.01)。尾部皮肤温度升高证实GABA注射有效抑制了中缝神经元。因此,当腹侧延髓中缝区域的神经元被激活时,它们会与HR同步增强房室传导、心室收缩力和舒张,但它们对心脏几乎没有或没有紧张性交感神经驱动作用。