Campbell H T, Lightfoot B O, Sklar A H
Department of Medicine, Medical College of Georgia, Augusta 30912-3140.
Proc Soc Exp Biol Med. 1988 Dec;189(3):317-24. doi: 10.3181/00379727-189-42813.
Atrial natriuretic peptide (ANP) is released from the cardiac atria in response to acute volume loads; when infused acutely ANP causes diuresis and natriuresis. Cyclic GMP (cGMP) appears to be the second messenger for ANP in the kidney. The role that ANP plays in the long-term regulation of salt and water balance is unclear, however, since resistance to ANP's natriuretic and diuretic activity develops during prolonged administration. The purpose of the present study is to examine the relationship between the rate of cGMP excretion in response to ANP and the development of resistance to ANP's diuretic and natriuretic activity. Following a 30-min baseline period of infusion of Ringer's solution conscious rats received ANP at 15 micrograms/kg/hr (n = 6) or Ringer's alone (n = 5) for 240 min. ANP-infused rats had a significant diuresis and natriuresis during the first hour of infusion; urinary cGMP excretion also increased compared to baseline. By 120 min after initiating the infusion in ANP-rats urinary volume and sodium excretion had declined to values not significantly different from those of baseline or control. In contrast, urinary cGMP excretion remained elevated for the duration of the ANP infusion, whether compared to baseline values or the control group. Resistance to the diuretic and natriuretic activity of ANP is not a result of mechanisms that involve cGMP generation.
心房利钠肽（ANP）在急性容量负荷时从心脏心房释放；急性输注ANP会导致利尿和利钠。环磷酸鸟苷（cGMP）似乎是ANP在肾脏中的第二信使。然而，ANP在盐和水平衡长期调节中的作用尚不清楚，因为在长期给药过程中会出现对ANP利钠和利尿活性的抵抗。本研究的目的是检查对ANP反应时cGMP排泄率与对ANP利尿和利钠活性抵抗的发展之间的关系。在30分钟的林格氏液输注基线期后，清醒大鼠以15微克/千克/小时的剂量接受ANP（n = 6）或仅接受林格氏液（n = 5），持续240分钟。输注ANP的大鼠在输注的第一个小时内出现显著的利尿和利钠；与基线相比，尿cGMP排泄也增加。在ANP大鼠开始输注后120分钟，尿量和钠排泄已降至与基线或对照组无显著差异的值。相比之下，无论与基线值还是对照组相比，在ANP输注期间尿cGMP排泄一直升高。对ANP利尿和利钠活性的抵抗不是涉及cGMP生成的机制的结果。
