Sigmon D H, Beierwaltes W H
Hypertension and Vascular Research Division, Ford Hospital, Detroit, MI 48202-2689.
Hypertension. 1994 Jan;23(1 Suppl):I34-9. doi: 10.1161/01.hyp.23.1_suppl.i34.
Endothelium-derived nitric oxide contributes to the regulation of regional blood flow. Inhibition of endothelium-derived nitric oxide synthesis increases blood pressure and vascular resistance. Using the substrate antagonist N omega-nitro-L-arginine-methyl ester to block endothelium-derived nitric oxide synthesis, we tested the hypothesis that, in two-kidney, one clip renovascular hypertension, endothelium-derived nitric oxide plays an increased role in maintaining blood flow to the nonclipped kidney and other visceral organs compared with normotensive controls. This could be due to increased vascular shear stress, a primary stimulus for endothelium-derived nitric oxide synthesis, after the onset of hypertension. In hypertensive rats with mild renal artery stenosis, basal renal blood flow normalized by kidney weight was similar in the nonclipped and clipped kidneys. Basal blood pressure of controls was 98 +/- 2 mm Hg compared with 145 +/- 3 mm Hg in the two-kidney, one clip hypertensive rats. N omega-nitro-L-arginine-methyl ester increased blood pressure by 20 +/- 2 and 43 +/- 3 mm Hg in control and hypertensive rats, respectively. Compared with normotensive controls, basal resistance was higher in all organ beds in the hypertensive rats including brain, heart, intestine, and kidney. With the exception of the renal circulation, the increase in vascular resistance after N omega-nitro-L-arginine-methyl ester was greater in hypertensive rats compared with normotensive controls. In the hypertensive rats, N omega-nitro-L-arginine-methyl ester caused a similar increase in vascular resistance in both the nonclipped and clipped kidneys, and this was not different from normotensive controls.(ABSTRACT TRUNCATED AT 250 WORDS)
内皮源性一氧化氮有助于调节局部血流。抑制内皮源性一氧化氮的合成会升高血压并增加血管阻力。我们使用底物拮抗剂Nω-硝基-L-精氨酸甲酯来阻断内皮源性一氧化氮的合成,以验证以下假设:在二肾一夹肾血管性高血压模型中,与正常血压对照组相比,内皮源性一氧化氮在维持未夹闭肾脏及其他内脏器官的血流方面发挥着更大的作用。这可能是由于高血压发作后血管剪切力增加,而血管剪切力是内皮源性一氧化氮合成的主要刺激因素。在轻度肾动脉狭窄的高血压大鼠中,按肾脏重量归一化后的基础肾血流量在未夹闭和夹闭的肾脏中相似。对照组的基础血压为98±2 mmHg,而二肾一夹高血压大鼠的基础血压为145±3 mmHg。Nω-硝基-L-精氨酸甲酯分别使对照大鼠和高血压大鼠的血压升高20±2 mmHg和43±3 mmHg。与正常血压对照组相比,高血压大鼠包括脑、心脏、肠道和肾脏在内的所有器官床的基础阻力均更高。除肾循环外,高血压大鼠在使用Nω-硝基-L-精氨酸甲酯后血管阻力的增加幅度大于正常血压对照组。在高血压大鼠中,Nω-硝基-L-精氨酸甲酯使未夹闭和夹闭的肾脏血管阻力产生相似的增加,且与正常血压对照组无差异。(摘要截选至250字)