Stevenson K M, Edgley A J, Bergström G, Worthy K, Kett M M, Anderson W P
Department of Physiology, Monash University, Clayton, Victoria, Australia. l
Hypertension. 2000 Nov;36(5):839-44. doi: 10.1161/01.hyp.36.5.839.
The effects on the renal vasculature and on arterial blood pressure of chronic infusion of low doses of angiotensin II (Ang II) into the renal artery were studied. Sprague Dawley rats were infused continuously with Ang II (0.5, 1.5, or 4.5 ng. kg(-1). min(-1)) or vehicle into the right renal artery (contralateral nephrectomy). Intrarenal Ang II infusion for 25 days produced dose-dependent rises (P:<0.001) in awake mean arterial pressure (111+/-1, 119+/-5, and 130+/-3 mm Hg in rats receiving 0.5, 1.5, and 4.5 ng. kg(-1). min(-1) Ang II, respectively) compared with 105+/-1 mm Hg (vehicle). Renal vessel lumen characteristics were assessed with an established, maximally dilated, isosmotic perfused kidney preparation. This revealed a small dose-dependent right shift in the pressure-flow relation (P=0.05), as well as a dose-dependent right shift and a dose-dependent reduction in the slope of the pressure-glomerular filtration rate relation (P=0.04 and 0.03, respectively). The effects of Ang II infusion on arterial pressure were not affected by the timing of the contralateral nephrectomy but were reduced when the contralateral kidney remained in situ. Acute losartan administration (10 mg/kg IV bolus) produced similar effects on arterial pressure in rats infused with vehicle or Ang II (4.5 ng. kg(-1). min(-1)) for 14 days, P=0.89), indicating the lack of systemic spillover of Ang II. Intraperitoneal Ang II (0.5, 1.5, or 4.5 ng. kg(-1). min(-1) for 25 days) had no effect on arterial pressure. Thus, chronic intrarenal infusion of low doses of Ang II resulted in changes in the renal vasculature compatible with dose-related structural reductions in the lumen diameter of preglomerular vessels and produced dose-related increases in arterial pressure.
研究了向肾动脉慢性输注低剂量血管紧张素II(Ang II)对肾血管系统和动脉血压的影响。将Sprague Dawley大鼠的右肾动脉(对侧肾切除)持续输注Ang II(0.5、1.5或4.5 ng·kg⁻¹·min⁻¹)或赋形剂。肾内输注Ang II 25天导致清醒平均动脉压出现剂量依赖性升高(P<0.001)(接受0.5、1.5和4.5 ng·kg⁻¹·min⁻¹ Ang II的大鼠分别为111±1、119±5和130±3 mmHg),而赋形剂组为105±1 mmHg。使用已建立的、最大扩张的、等渗灌注肾制备方法评估肾血管腔特征。这显示压力-流量关系出现小的剂量依赖性右移(P=0.05),以及压力-肾小球滤过率关系出现剂量依赖性右移和剂量依赖性斜率降低(分别为P=0.04和0.03)。输注Ang II对动脉压的影响不受对侧肾切除时间的影响,但当对侧肾保留原位时作用减弱。急性给予氯沙坦(10 mg/kg静脉推注)对输注赋形剂或Ang II(4.5 ng·kg⁻¹·min⁻¹)14天的大鼠的动脉压产生相似影响(P=0.89),表明不存在Ang II的全身溢出。腹腔内给予Ang II(0.5、1.5或4.5 ng·kg⁻¹·min⁻¹,持续25天)对动脉压无影响。因此,慢性肾内输注低剂量Ang II导致肾血管系统发生变化,与肾小球前血管腔直径的剂量相关结构减少相符,并导致动脉压出现剂量相关升高。