RENAL RESPONSE TO URODILATIN IN HEART FAILURE

尿扩张素(Uro-ANP95-126)是该家族的一个新成员 利钠多肽。它与ANP99-126具有相同的结构，具有 氨基末端有四个额外的氨基酸。很可能，乌罗是 起源于肾脏并分泌到尿液中。Uro比ANF有更强的利钠作用 低剂量。 我们研究了1)外源性输注尿素和尿液对肾脏的影响 ANP99-126在充血性心力衰竭诱导前后的变化 (2)大鼠主动脉-下腔静脉瘘(ACF)的作用 使用中性内切酶抑制剂(NEP-I)，SQ28,063 3)NEP-I和NEP-I对大鼠肾脏的影响 C-ANF4-23阻断心钠素清除受体对~(125)I-R代谢的影响 ANP99-126和125I-URO。 在对照组大鼠中，URO(0.75-12微克/公斤/小时)引起剂量依赖性增加 尿流率(V)、绝对尿流率(UNaV)和钠排泄分数 (Fena%)。肾小球滤过率(GFR)显著上升，尽管 平均动脉压(MAP)明显降低。相同剂量的输液 尿酸对心力衰竭大鼠V、GFR、UNaV的影响 和Fena%，但利尿和利钠的绝对水平是 充血性心力衰竭大鼠较低。向ACF大鼠体内注入尿素时的情况 NEP-I(40 mg/kg)预处理后的绝对尿流量和钠 排泄量与对照组大鼠无明显差异。 等摩尔剂量的ANP 99-126注入对照组大鼠 利尿剂和利钠反应，比获得的反应要小 输注尿素后。同样，充血性心力衰竭的大鼠表现出减弱的 对ANP99-126的肾脏反应与其显著的肾脏反应进行比较 等摩尔剂量的尿素。这些不同之处在于利钠药 ANP和Uro的效力，可能归因于我们的发现，虽然ANP 被NEP和ANP清除受体Uro从循环中移除 主要由后者去除。

Urodilatin (URO - ANP95-126), is a newly described member of the family of natriuretic peptides. It has the same structure as ANP99-126 with four additional amino acids on the amino terminal end. Likely, URO is of renal origin and secreted into urine. URO is more natriuretic than ANF at low doses. We investigated 1) The renal effects of exogenous infusion of URO and ANP99-126 before and after the induction of congestive heart failure (CHF) by creation of an aortocaval fistula (ACF) in rats, 2) The effects of pretreatment with neutral endopeptidase inhibitor (NEP-I), SQ28,063 on the renal response to URO in these rats, and 3) The effect of NEP-I and ANP clearance receptor blockade by C-ANF4-23 on the metabolism of 125I- ANP99-126 and 125I-URO. In control rats URO (0.75-12 microg/kg/h) caused dose dependent increases in urine flow (V), and absolute (UNaV) and fractional sodium excretion (FENa%). Glomerular filtration rate (GFR) rose significantly despite markedly lower mean arterial pressure (MAP). Infusion of the same doses of URO to rats with CHF induced significant increases in V, GFR, UNaV and FENa%, however the absolute levels of diuresis and natriuresis were lower in rats with CHF. When URO was infused into rats with ACF pretreated with NEP-I (40 mg/kg) the absolute urine flow and sodium excretion were not different from those obtained in control rats. Infusion of equimolar doses of ANP 99-126 into control rats resulted in diuretic and natriuretic response, which were smaller than those obtained after infusion of URO. Similarly, rats with CHF showed an attenuated renal response to ANP99-126, compared to their remarkable renal response to equimolar doses of URO. These differences between the natriuretic potency of ANP and URO, may be attributed to our findings that while ANP is removed from the circulation by NEP and ANP clearance receptors, URO is removed mainly by the latter.