Li Q, Dale W E, Hasser E M, Blaine E H
Dalton Cardiovascular Research Center, University of Missouri, Columbia 65211, USA.
Am J Physiol. 1996 Jul;271(1 Pt 2):R200-7. doi: 10.1152/ajpregu.1996.271.1.R200.
We examined the mechanisms mediating hypertension in conscious rats during acute and chronic infusion of angiotensin II (ANG II) at pressor doses (50, 100, and 200 ng.kg-1.min-1). Trimethaphan-induced blood pressure reduction was inversely related to the acute dose of ANG II, consistent with a constrictor action of ANG II on vascular smooth muscle and withdrawal of sympathetic tone. During chronic ANG II infusion, the entire increase in mean arterial pressure (MAP) was inhibited by trimethaphan, consistent with neural mediation. During acute ANG II hypertension, the AT1-specific receptor blocker losartan induced a large fall in MAP (64 +/- 4 mmHg) in ganglion-blocked (chlorisondamine) rats, whereas, during chronic ANG II hypertension, losartan had only a small hypotensive effect (11 +/- 3 mmHg). To determine the time course of the change from vascular smooth muscle action to neural action, we measured MAP in response to trimethaphan during the first 24 h of ANG II infusion. After 5 h, the minimal MAP in response to trimethaphan was significantly higher than that before ANG II. After 10 h of infusion, trimethaphan decreased MAP to pre-ANG II levels. That is, the neural component was fully active after only 10 h of infusion in rats. Finally, chronic administration of ANG II resulted in a dose-related increase in MAP that, at all doses, was completely inhibited by trimethaphan. These findings are consistent with ANG II acting primarily on vascular smooth muscle during acute infusion and via neural pathways during chronic treatment. The transition from direct smooth muscle to indirect neural action is rapid in rats (< 10 h), and the MAP and neural responses to ANG II are dose related during chronic hypertension.
我们研究了在清醒大鼠中，以升压剂量（50、100和200 ng·kg⁻¹·min⁻¹）急性和慢性输注血管紧张素II（ANG II）时介导高血压的机制。三甲噻方诱导的血压降低与ANG II的急性剂量呈负相关，这与ANG II对血管平滑肌的收缩作用以及交感神经张力的降低一致。在慢性ANG II输注期间，三甲噻方抑制了平均动脉压（MAP）的全部升高，这与神经介导作用一致。在急性ANG II高血压期间，AT1特异性受体阻滞剂氯沙坦在神经节阻断（氯筒箭毒碱）大鼠中引起MAP大幅下降（64±4 mmHg），而在慢性ANG II高血压期间，氯沙坦只有轻微的降压作用（11±3 mmHg）。为了确定从血管平滑肌作用转变为神经作用的时间进程，我们在ANG II输注的前24小时内测量了对三甲噻方的MAP反应。5小时后，对三甲噻方的最小MAP显著高于ANG II输注前。输注10小时后，三甲噻方将MAP降至ANG II输注前水平。也就是说，在大鼠中仅输注10小时后神经成分就完全活跃了。最后，ANG II的慢性给药导致MAP呈剂量相关增加，在所有剂量下，均被三甲噻方完全抑制。这些发现与ANG II在急性输注期间主要作用于血管平滑肌，而在慢性治疗期间通过神经途径起作用一致。在大鼠中从直接平滑肌作用到间接神经作用的转变很快（<10小时），并且在慢性高血压期间对ANG II的MAP和神经反应与剂量相关。
