Sahai A, Ganguly P K
Division of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Clin Auton Res. 1993 Apr;3(2):137-43. doi: 10.1007/BF01818999.
The relationship between atrial natriuretic peptide (ANP) and peripheral sympathetic nervous system function was studied in diabetic and hypertensive rats. Animals were studied in diabetic and hypertensive rats. Animals were divided into four groups: control, diabetic, hypertensive and diabetic plus hypertensive. Diabetes was induced by streptozotocin (65 mg/kg) injection and hypertension by abdominal aortic constriction. Studies were performed at 1 and 6 weeks. Plasma ANP was increased at 1 week in all groups except controls. Noradrenaline turnover, an index of sympathetic activity in kidney, was attenuated in all pathological groups unlike controls. These changes were associated with increased activity of Ca2++Mg2+ ATPase, which is known to serve as a Ca2+ pump in kidney cortex basolateral membrane. In contrast, at 6 weeks, Ca2++Mg2+ ATPase was significantly decreased only in the diabetic plus hypertensive group which also showed signs of congestive heart failure, increased sympathetic activity and decreased plasma ANP levels. Intracerebral microdialysis of the extracellular space around the paraventricular nucleus (PVN) of the hypothalamus showed a decreased concentration of ANP in the diabetic plus hypertensive group. Infusion of ANP and pentolinium, a ganglionic blocker in diabetic plus hypertensive Ca2+ restored pump activity towards control values; ANP alone had no effect. Our results indicate decreased plasma ANP levels, increased sympathetic drive and a depressed kidney Ca2+ pump in diabetic plus hypertensive rats with heart failure. The relationships between these factors, and the potential modulating role of ANP is discussed.
在糖尿病大鼠和高血压大鼠中研究了心房利钠肽(ANP)与外周交感神经系统功能之间的关系。对糖尿病大鼠和高血压大鼠进行了研究。动物被分为四组:对照组、糖尿病组、高血压组和糖尿病合并高血压组。通过注射链脲佐菌素(65mg/kg)诱导糖尿病,通过腹主动脉缩窄诱导高血压。在1周和6周时进行研究。除对照组外,所有组在1周时血浆ANP均升高。与对照组不同,所有病理组中作为肾脏交感神经活动指标的去甲肾上腺素周转率均降低。这些变化与Ca2++Mg2+ATP酶活性增加有关,已知该酶在肾皮质基底外侧膜中作为Ca2+泵发挥作用。相比之下,在6周时,仅糖尿病合并高血压组的Ca2++Mg2+ATP酶显著降低,该组还表现出充血性心力衰竭的迹象、交感神经活动增加和血浆ANP水平降低。对下丘脑室旁核(PVN)周围细胞外间隙进行脑内微透析显示,糖尿病合并高血压组中ANP浓度降低。在糖尿病合并高血压大鼠中输注ANP和神经节阻滞剂潘托铵可使Ca2+泵活性恢复至对照值;单独输注ANP则无作用。我们的结果表明,在伴有心力衰竭的糖尿病合并高血压大鼠中,血浆ANP水平降低、交感神经驱动力增加且肾Ca2+泵功能受抑制。讨论了这些因素之间的关系以及ANP的潜在调节作用。