Koeners M P, Racasan S, Koomans H A, Joles J A, Braam B
Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands.
Acta Physiol (Oxf). 2007 Aug;190(4):329-38. doi: 10.1111/j.1748-1761.2007.01702.x. Epub 2007 May 30.
Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation.
Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. Nomega-nitro-l-arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic).
Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 +/- 4 vs. 33 +/- 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 +/- 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed.
Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation.
一氧化氮（NO）和超氧化物被认为在肾血流量（RBF）自身调节中起调节作用，因此可能与高血压的发生有关。为了扩展我们之前的观察结果，即自发性高血压大鼠（SHR）中动态NO释放受损，我们首先研究了SHR中RBF自身调节对超氧化物的依赖性是否增加，其次研究了围产期补充对SHR的有益作用是否部分是由于早期纠正了RBF自身调节。我们假设围产期补充通过恢复动态NO释放和/或降低对超氧化物的依赖性，将改善终身血压调节。
在静脉注射N-ω-硝基-L-精氨酸（NO合酶抑制剂）或tempol（超氧化物歧化酶模拟物）之前和期间，通过逐步降低麻醉雄性SHR、围产期补充精氨酸和抗氧化剂的SHR（SHRsuppl）以及Wistar-Kyoto（WKY）大鼠的肾灌注压来研究自身调节。
与WKY相比，自发性高血压大鼠表现出更宽的RBF自身调节工作范围（分别为59±4与33±2 mmHg；P<0.01）。SHR的围产期补充降低了平均动脉压、肾血管阻力和RBF自身调节的工作范围（43±3 mmHg；P<0.01）。此外，自身调节效率降低。RBF自身调节特征向正常血压的WKY转变。然而，动态NO释放仍然受损，并且在各组之间未观察到RBF自身调节对超氧化物的依赖性有明显差异。
围产期补充使SHR的RBF自身调节特征向WKY转变，尽管SHRsuppl肾调节NO产生以应对剪切应力的能力似乎仍然受损。在围产期补充的SHR中观察到的对RBF的控制较不严格，可能导致长期血压控制得到改善。这可能部分是围产期补充有益作用的基础。
