Pflueger A C, Larson T S, Hagl S, Knox F G
Departments of Medicine and Physiology and Biophysics, Division of Nephrology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Am J Physiol. 1999 Sep;277(3):R725-33. doi: 10.1152/ajpregu.1999.277.3.R725.
The role of nitric oxide (NO) in the regulation of the intrarenal microcirculation in streptozotocin (STZ)-induced diabetes mellitus in rats is not clear. We examined renal cortical and papillary hemodynamics in STZ rats and determined the effects of systemic inhibition and stimulation of NO synthesis. Renal blood flow in cortical (QCC), and inner medullary ascending (QAV) and descending (QDV) vasa recta capillaries was measured by fluorescence videomicroscopy in STZ Munich-Wistar rats and nondiabetic control rats. Ten days after STZ injection (80 mg/kg ip), basal QCC and QDV were significantly greater in STZ rats (n = 16) compared with control rats (n = 15). Infusion of N(G)-monomethyl-L-arginine (L-NMMA, 15 mg/kg bolus, 500 microg. min(-1). kg(-1) iv) decreased Q(CC) (-41%), QAV (-38%), and QDV (-37%) in control rats (n = 6) and to a significantly greater magnitude than in STZ rats (n = 7), Q(CC) (-14%), QAV (-20%), and QDV (-25%). Coinfusion of L-arginine (L-Arg, 1 mg. kg(-1). min(-1) iv) with L-NMMA increased Q(CC) to a significantly greater extent (P < 0.01) in control rats compared with STZ rats. In subsequent studies, infusion of L-Arg alone increased QCC (+50%), QAV (+16%), and QDV (+11%) in control rats (n = 5) but had no effect in STZ rats (n = 5). These results show that the response of renal cortical and papillary capillary blood flow to both inhibition and stimulation of NO synthesis is attenuated in the early onset of STZ-diabetes mellitus rats compared with control rats.
一氧化氮(NO)在链脲佐菌素(STZ)诱导的大鼠糖尿病肾内微循环调节中的作用尚不清楚。我们研究了STZ大鼠的肾皮质和乳头血流动力学,并确定了全身抑制和刺激NO合成的作用。通过荧光视频显微镜测量了STZ慕尼黑-威斯塔大鼠和非糖尿病对照大鼠皮质肾血流量(QCC)、髓质内直小血管升支(QAV)和降支(QDV)的血流量。注射STZ(80mg/kg,腹腔注射)10天后,与对照大鼠(n = 15)相比,STZ大鼠(n = 16)的基础QCC和QDV显著更高。在对照大鼠(n = 6)中,输注N(G)-单甲基-L-精氨酸(L-NMMA,15mg/kg推注,500μg·min⁻¹·kg⁻¹,静脉注射)可使Q(CC)降低41%、QAV降低38%、QDV降低37%,且降低幅度显著大于STZ大鼠(n = 7),其Q(CC)降低14%、QAV降低20%、QDV降低25%。L-精氨酸(L-Arg,1mg·kg⁻¹·min⁻¹,静脉注射)与L-NMMA共同输注时,与STZ大鼠相比,对照大鼠的Q(CC)增加幅度显著更大(P < 0.01)。在随后的研究中,单独输注L-Arg可使对照大鼠(n = 5)的QCC增加50%、QAV增加16%、QDV增加11%,但对STZ大鼠(n = 5)无影响。这些结果表明,与对照大鼠相比,STZ糖尿病大鼠早期肾皮质和乳头毛细血管血流对NO合成抑制和刺激的反应减弱。