Levels of interstitial norepinephrine in the heart and kidney during the development of hypertensive heart failure

交感神经活动增加在心力衰竭的发展过程中起着重要作用。以前的研究，使用放射性同位素或交感神经活动的直接记录，已经表明在衰竭的心脏和肾脏中交感神经活动增加。在本研究中，在出现高血压心力衰竭之前，测定了清醒的达尔盐敏感性（DS）和盐抵抗性（DR）大鼠心脏和肾脏间质去甲肾上腺素（iNE）水平。大鼠从6周龄开始喂食高盐饮食。在戊巴比妥麻醉下，将微透析探针（8 mm长，0.2 mm内径，50，000分子量截止）插入LV游离壁和肾脏中。手术恢复后（48小时后），用林格氏溶液灌注透析探针，并在清醒动物中测定NE水平。DS大鼠发生高血压和心脏肥大，左心室（LV）收缩功能保留，即，代偿性左心室肥大，在12周龄时。相反，DR大鼠没有发生高血压。DS大鼠心脏和肾脏的iNE水平均显著高于DR大鼠。间歇吸入13%CO_2可使DS和DR大鼠心、肾iNE增加，但DS大鼠心、肾iNE增加幅度更大。此外，在停止高碳酸血症应激后，DS大鼠心脏和肾脏中增加的iNE的恢复明显延长。相反，DR大鼠iNE迅速下降至对照水平。因此，高血压大鼠心力衰竭前交感神经对短暂应激的超敏反应和iNE的长期升高可能有助于心力衰竭的发展。在应激期间和之后，在心脏和肾脏中观察到异常升高的iNE水平。

Increased sympathetic nerve activity plays an important role during the development of heart failure. Previous studies, using radioisotopes or direct recordings of sympathetic nerve activity, have shown an increase in sympathetic nerve activity in a failing heart as well as its kidney. In the present study, levels of interstitial norepinephrine (iNE) of heart and kidney were determined in conscious Dahl salt-sensitive (DS) and salt-resistant (DR) rats before developing hypertensive heart failure. Rats were fed a high-salt diet from 6 weeks of age. Under pentobarbital anesthesia, the microdialysis probes (8 mm length, 0.2 mm inner diameter, 50,000 molecular weight cutoff) were inserted into LV free wall and kidney. After a recovery from the surgery (48 hours later), the dialysis probes were perfused with Ringer's solution and NE levels were determined in conscious animals. DS rats developed hypertension and cardiac hypertrophy with preserved left ventricular (LV) systolic function, i.e., compensated LV hypertrophy, at 12 weeks of age. In contrast, DR rats did not develop hypertension. Levels of iNE in DS rats were significantly greater in both heart and kidney than in DR rats. The intermittent inhalation of 13% CO2 gas increased cardiac and renal iNE of both DS and DR rats, but its increase was much greater in both organs of DS rats. Moreover, the recovery of increased iNE after the cessation of hypercapnia stress was markedly prolonged in the heart and kidney of DS rats. In contrast, iNE in DR rats quickly reduced to the control levels. Thus, a hypersensitive response of sympathetic nerve to the transient stress and prolonged elevation of iNE in a hypertensive rat before heart failure might contribute to the development of heart failure. Abnormally elevated iNE levels during and after stress were seen in a heart as well as a kidney.