Stevens T L, Rasmussen T E, Wei C M, Kinoshita M, Matsuda Y, Burnett J C
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
J Card Fail. 1996 Jun;2(2):119-25. doi: 10.1016/s1071-9164(96)80030-3.
Atrial and brain natriuretic peptides exert renal and cardiovascular actions through binding to the natriuretic peptide-A receptor, while C-type natriuretic peptide mediates actions that occur through binding to the natriuretic peptide-B receptor, with subsequent generation of cyclic guanosine monophosphate. This study determined responses of circulating atrial natriuretic peptides in experimental acute heart failure and addressed the hypothesis that elevated circulating atrial natriuretic peptides serve a homeostatic role in regulating sodium excretion and that this action is localized to the glomerulus and distal nephron, sites rich in natriuretic peptide-A receptors.
Studies were performed in the absence and presence of HS-142-1, an inhibitor of the natriuretic peptide receptors. Two groups of anesthetized dogs underwent induction of acute heart failure by rapid ventricular pacing, as characterized by decreases in cardiac output and increases in filling pressures with associated elevation of endogenous atrial natriuretic peptides secondary to increases in atrial stretch. In group 1 (n = 5, vehicle intrarenal bolus), despite acute heart failure-mediated decreases in cardiac output, sodium excretion was preserved with maintenance of the glomerular filtration rate and distal fractional sodium reabsorption. In group 2 (n = 5), in response to the natriuretic peptide receptor antagonist, HS-142-1 (0.5 mg/kg intrarenal bolus), sodium excretion (17.0 +/- 4.4 to 5.9 +/- 3.2 microEq/min; P < .05) and glomerular filtration rate decreased (33.0 +/- 3.6 to 21.0 +/- 3.9 mL/min; P < .05) and distal fractional sodium reabsorption increased (98.0 +/- 0.63 to 99.3 +/- 0.25%; P < .05), in association with a decrease in plasma cyclic guanosine monophosphate (13.0 +/- 3.5 to 6.6 +/- 2.9 pmol/mL; P < .05) and renal cyclic guanosine monophosphate generation (1,216 +/- 421 to 466 +/- 208 pmol/min; P < .05).
This study supports a functionally significant role for the endogenous natriuretic peptide system in preserving sodium homeostasis and glomerular filtration rate in acute heart failure.
心房利钠肽和脑利钠肽通过与利钠肽-A受体结合发挥肾脏和心血管作用，而C型利钠肽通过与利钠肽-B受体结合介导相关作用，随后生成环磷酸鸟苷。本研究测定了实验性急性心力衰竭时循环心房利钠肽的反应，并探讨了以下假说：循环心房利钠肽升高在调节钠排泄中发挥稳态作用，且该作用定位于富含利钠肽-A受体的肾小球和远端肾单位。
在使用和不使用利钠肽受体抑制剂HS-142-1的情况下进行研究。两组麻醉犬通过快速心室起搏诱导急性心力衰竭，其特征为心输出量降低、充盈压升高，且由于心房牵张增加导致内源性心房利钠肽升高。在第1组（n = 5，肾内注射载体）中，尽管急性心力衰竭介导的心输出量降低，但钠排泄得以维持，肾小球滤过率和远端钠重吸收分数保持不变。在第2组（n = 5）中，给予利钠肽受体拮抗剂HS-142-1（0.5 mg/kg肾内注射）后，钠排泄（从17.0±4.4降至5.9±3.2微当量/分钟；P <.05）和肾小球滤过率降低（从33.0±3.6降至21.0±3.9毫升/分钟；P <.05），远端钠重吸收分数增加（从98.0±0.63升至99.3±0.25%；P <.05），同时血浆环磷酸鸟苷降低（从13.0±3.5降至6.6±2.9皮摩尔/毫升；P <.05），肾环磷酸鸟苷生成减少（从1216±421降至466±208皮摩尔/分钟；P <.05）。
本研究支持内源性利钠肽系统在急性心力衰竭时维持钠稳态和肾小球滤过率方面具有重要功能作用。
