Spradley Frank T, White John J, Paulson William D, Pollock David M, Pollock Jennifer S
Section of Experimental Medicine, Georgia Regents University Augusta, Georgia ; Department of Medicine, Georgia Regents University Augusta, Georgia.
Department of Medicine, Georgia Regents University Augusta, Georgia ; Charlie Norwood VA Medical Center, Georgia Regents University Augusta, Georgia.
Physiol Rep. 2013 Nov;1(6):e00145. doi: 10.1002/phy2.145. Epub 2013 Nov 5.
Chronic renal failure (CRF) is associated with hypertension and concomitant endothelial dysfunction, enhanced vasoconstriction, and nitric oxide synthase (NOS) dysfunction. Vascular function in patients is assessed in peripheral extremity arteries like the finger arteries, whereas animal studies often use the centrally located aorta. Therefore, we examined whether peripheral tail artery and aortic NOS function are differentially regulated by blood pressure in rats with CRF. Using wire myography, arterial function was assessed in 16-week-old Sprague-Dawley rats that were subjected to 5/6 nephrectomy (Nx; arterial ligation model) 8 weeks earlier or non-Nx (control) rats. In aortas from Nx rats, endothelial-dependent vasorelaxation response to acetylcholine (ACh) was blunted and there was enhancement of phenylephrine (PE)-mediated vasoconstriction. Inversely, tail arteries from Nx rats had no change in endothelial function and reduced response to PE. Studies where arterial segments were incubated with the nonspecific NOS inhibitor, L-NAME, showed that Nx reduced NOS function in the aorta but increased NOS function in tail artery for both ACh and PE responses. Furthermore, the observed alterations in NOS function in both aorta and tail artery were abolished when mean arterial blood pressure, as assessed by telemetry, was maintained at normal levels in the 5/6 Nx rats using triple therapy: hydralazine (30 mg/kg per day), hydrochlorothiazide (10 mg/kg per day), and reserpine (0.5 mg/kg per day). In conclusion, differential changes of NOS function in central versus peripheral arteries in CRF are dependent upon hypertension.
慢性肾衰竭（CRF）与高血压以及伴随的内皮功能障碍、血管收缩增强和一氧化氮合酶（NOS）功能障碍相关。患者的血管功能在外周动脉如手指动脉中进行评估，而动物研究通常使用位于中央的主动脉。因此，我们研究了CRF大鼠外周尾动脉和主动脉的NOS功能是否受血压的不同调节。使用线肌张力测定法，在8周前接受5/6肾切除术（Nx；动脉结扎模型）的16周龄Sprague-Dawley大鼠或非Nx（对照）大鼠中评估动脉功能。在Nx大鼠的主动脉中，对乙酰胆碱（ACh）的内皮依赖性血管舒张反应减弱，去氧肾上腺素（PE）介导的血管收缩增强。相反，Nx大鼠的尾动脉内皮功能无变化，对PE的反应降低。将动脉段与非特异性NOS抑制剂L-NAME孵育的研究表明，Nx降低了主动脉中的NOS功能，但增加了尾动脉中对ACh和PE反应的NOS功能。此外，当使用三联疗法（肼屈嗪，30mg/kg/天；氢氯噻嗪，10mg/kg/天；利血平，0.5mg/kg/天）将5/6 Nx大鼠通过遥测评估的平均动脉血压维持在正常水平时，主动脉和尾动脉中观察到的NOS功能改变被消除。总之，CRF中中央动脉与外周动脉NOS功能的差异变化取决于高血压。
