Hildebrandt D A, Mizelle H L, Brands M W, Hall J E
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216.
Am J Physiol. 1992 Mar;262(3 Pt 2):R395-9. doi: 10.1152/ajpregu.1992.262.3.R395.
A 32-amino acid atrial natriuretic peptide (ANP)-like peptide, putatively synthesized by the kidney, has recently been isolated from human urine. This peptide, urodilatin (Uro), is structurally similar to the 28-amino acid ANP, suggesting that they might have similar actions on renal fluid and electrolyte excretion. The purpose of this study was to characterize the direct renal actions of low doses of Uro infusion and to compare them with the effects of equimolar intrarenal infusions of either ANP or the 24-amino acid atriopeptin III (AP III). Synthetic Uro was infused into the renal artery of pentobarbital sodium-anesthetized mongrel dogs (n = 8) at 0.14, 0.28, and 1.43 pmol.kg-1.min-1 while renal perfusion pressure was servo-controlled at 100 mmHg. Uro infusion at 1.43 pmol.kg-1.min-1 increased sodium excretion from an average control of 57.4 +/- 10.1 to 159.0 +/- 24.4 mueq/min. Uro infusion at the highest dose also increased potassium excretion (28.0 +/- 4.5 vs. 40.4 +/- 7.4 mueq/min), chloride excretion (56 +/- 11 vs. 155 +/- 22 mueq/min), and urine volume (0.54 +/- 0.12 vs. 1.22 +/- 0.25 ml/min). Fractional lithium excretion, a marker for proximal tubular sodium reabsorption, was not altered by Uro infusion, nor were urinary guanosine 3',5'-cyclic monophosphate excretion, glomerular filtration rate, or effective renal plasma flow changed. Equimolar infusions of these low doses of either alpha human ANP (n = 6) or AP III (n = 8) had no effect on any of the measured variables. Thus, within the range of doses used in this study, Uro was a more effective natriuretic and diuretic agent than either ANP or AP III.(ABSTRACT TRUNCATED AT 250 WORDS)
一种由肾脏假定合成的含32个氨基酸的心房利钠肽(ANP)样肽,最近已从人尿中分离出来。这种肽,即尿钠素(Uro),在结构上与含28个氨基酸的ANP相似,这表明它们可能对肾液体和电解质排泄有相似的作用。本研究的目的是描述低剂量输注Uro的直接肾脏作用,并将其与等摩尔肾内输注ANP或含24个氨基酸的心房肽III(AP III)的作用进行比较。将合成的Uro以0.14、0.28和1.43 pmol·kg⁻¹·min⁻¹的剂量注入戊巴比妥钠麻醉的杂种犬(n = 8)的肾动脉,同时将肾灌注压伺服控制在100 mmHg。以1.43 pmol·kg⁻¹·min⁻¹的剂量输注Uro可使钠排泄量从平均对照值57.4±10.1增加到159.0±24.4μeq/min。最高剂量的Uro输注也增加了钾排泄(28.0±4.5对40.4±7.4μeq/min)、氯排泄(56±11对155±22μeq/min)和尿量(0.54±0.12对1.22±0.25 ml/min)。锂排泄分数,近端肾小管钠重吸收的标志物,不受Uro输注的影响,尿鸟苷3',5'-环磷酸排泄、肾小球滤过率或有效肾血浆流量也未改变。等摩尔输注这些低剂量的α人ANP(n = 6)或AP III(n = 8)对任何测量变量均无影响。因此,在本研究使用的剂量范围内,Uro是比ANP或AP III更有效的利钠和利尿剂。(摘要截断于250字)