Lafferty H M, Gunning M, Silva P, Zimmerman M B, Brenner B M, Anderson S
Renal Division, Brigham and Women's Hospital, Boston, MA 02115.
Circ Res. 1989 Sep;65(3):640-6. doi: 10.1161/01.res.65.3.640.
To investigate the in vivo effects of inhibition of endopeptidase 24.11, an enkephalinase enzyme shown to be involved in atrial natriuretic peptide (ANP) breakdown in vitro, we infused phosphoramidon, a specific inhibitor of endopeptidase 24.11, into rats with reduced renal mass (and chronic extracellular volume expansion) and into normal rats. Relative to baseline values in rats with remnant kidneys, phosphoramidon led to elevations of plasma ANP levels and concomitant increases in urinary sodium excretion, fractional excretion of sodium, glomerular filtration rate, filtration fraction, and urinary cyclic GMP excretion. Similar changes in renal function and urinary cyclic GMP excretion were obtained with thiorphan, another endopeptidase 24.11 inhibitor. These enhanced ANP levels and renal actions were not observed with phosphoramidon in normal rats. These results show that plasma ANP levels can be modulated in rats with reduced renal mass by inhibition of endopeptidase 24.11.
为研究抑制内肽酶24.11的体内效应，内肽酶24.11是一种在体外实验中显示参与心房利钠肽（ANP）分解的脑啡肽酶，我们将内肽酶24.11的特异性抑制剂膦甲脒注入肾质量减少（伴有慢性细胞外液量增加）的大鼠以及正常大鼠体内。相对于残余肾大鼠的基线值，膦甲脒导致血浆ANP水平升高，并伴随尿钠排泄、钠分数排泄、肾小球滤过率、滤过分数及尿环磷酸鸟苷排泄增加。另一种内肽酶24.11抑制剂硫磷酰胺也使肾功能及尿环磷酸鸟苷排泄出现类似变化。在正常大鼠中，膦甲脒未引起这些变化。这些结果表明，抑制内肽酶24.11可调节肾质量减少大鼠的血浆ANP水平。
