Mattson D L, Raff H, Roman R J
Department of Physiology, Medical College of Wisconsin 53226.
Am J Physiol. 1991 Jun;260(6 Pt 2):R1200-9. doi: 10.1152/ajpregu.1991.260.6.R1200.
This study examined whether angiotensin II (ANG II) influences the pressure-natriuretic (PN) response by altering renal cortical or medullary hemodynamics. Studies were performed in Inactin-anesthetized rats that were acutely volume expanded to maintain plasma renin activity and ANG II levels in the physiological range. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of norepinephrine, vasopressin, cortisol, and aldosterone were fixed by intravenous infusion. In control rats (n = 8), sodium excretion increased from 3 to 17 microeq.min-1.g kidney wt-1 as renal perfusion pressure (RPP) was elevated from 96 to 141 mmHg (n = 8). Captopril (2 mg/kg, n = 9) reduced plasma levels of ANG II from 48 +/- 5 to 18 +/- 2 pg/ml, but it did not alter the PN relationship. Infusion of ANG II (20 ng.kg-1.min-1, n = 9) increased plasma levels of ANG II to 232 +/- 42 pg/ml and shifted the PN relationship to the right by 14 mmHg. Captopril increased renal blood flow, and infusion of ANG II returned it to control. Captopril had no effect on glomerular filtration rate (GFR) or glomerular capillary pressure (Pglom); however, subsequent ANG II infusion decreased Pglom from 56 +/- 2 to 48 +/- 2 mmHg and reduced GFR by 30%. Neither captopril nor ANG II altered papillary bloodflow or vasa recta capillary pressure at normal levels of RPP. These results indicate that the shift of the PN relationship during infusion of ANG II is due to a decrease in filtered load and enhanced tubular reabsorption of sodium. Acute blockade of the renin-angiotensin system had little effect on the PN response in volume-expanded rats despite affecting renal hemodynamics, because either the plasma and/or intrarenal levels of ANG II were already suppressed below those needed to influence tubular function or volume expansion inhibits tubular reabsorption in the nephron segments normally influenced by ANG II.
本研究检测了血管紧张素II(ANG II)是否通过改变肾皮质或髓质血流动力学来影响压力利尿(PN)反应。研究在经Inactin麻醉的大鼠中进行,这些大鼠被急性扩容以维持血浆肾素活性和ANG II水平在生理范围内。通过肾去神经支配消除对肾脏的神经影响,并通过静脉输注使去甲肾上腺素、血管加压素、皮质醇和醛固酮的血浆水平固定。在对照大鼠(n = 8)中,随着肾灌注压(RPP)从96 mmHg升高至141 mmHg(n = 8),钠排泄量从3微当量·分钟-1·克肾重-1增加至17微当量·分钟-1·克肾重-1。卡托普利(2毫克/千克,n = 9)使ANG II的血浆水平从48±5皮克/毫升降至18±2皮克/毫升,但未改变PN关系。输注ANG II(20纳克·千克-1·分钟-1,n = 9)使ANG II的血浆水平升高至232±42皮克/毫升,并使PN关系右移14 mmHg。卡托普利增加肾血流量,输注ANG II后使其恢复至对照水平。卡托普利对肾小球滤过率(GFR)或肾小球毛细血管压力(Pglom)无影响;然而,随后输注ANG II使Pglom从56±2 mmHg降至48±2 mmHg,并使GFR降低30%。在正常RPP水平下,卡托普利和ANG II均未改变乳头血流或直小血管毛细血管压力。这些结果表明,输注ANG II期间PN关系的改变是由于滤过负荷降低和肾小管对钠的重吸收增强所致。尽管影响肾血流动力学,但急性阻断肾素-血管紧张素系统对容量扩张大鼠的PN反应影响很小,这是因为ANG II的血浆和/或肾内水平已被抑制至低于影响肾小管功能所需的水平,或者容量扩张抑制了通常受ANG II影响的肾单位节段中的肾小管重吸收。