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，测定了有意识的达尔盐敏感（DS）和盐抵抗（DR）大鼠发生高血压心力衰竭前心脏和肾脏间质去甲肾上腺素（iNE）的水平。大鼠从6周龄开始饲喂高盐饮食。在戊巴比妥麻醉下，将微透析探针（长度8 mm，内径0.2 mm，截分子量5万）分别插入左室游离壁和肾脏。手术恢复后（48小时后），透析探针灌注林格氏液，并在清醒的动物中测定NE水平。DS大鼠在12周龄时出现高血压和心脏肥厚，左室收缩功能保留，即代偿性左室肥厚。相比之下，DR大鼠没有发生高血压。DS大鼠心脏和肾脏的iNE水平明显高于DR大鼠。间歇性吸入13% CO2气体使DS大鼠和DR大鼠的心脏和肾脏的iNE增加，但DS大鼠的两个器官的iNE增加要大得多。此外，停止高糖血症应激后，DS大鼠心脏和肾脏中iNE升高的恢复时间明显延长。相比之下，DR大鼠的iNE迅速降低到对照水平。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延长的iNE升高可能有助于心力衰竭的发展。在压力期间和之后，在心脏和肾脏中都发现了异常升高的肾上腺素水平。

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.