Wang D H, Du Y
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1065, USA.
J Hypertens. 1998 Apr;16(4):467-75. doi: 10.1097/00004872-199816040-00008.
To test the hypotheses that a high sodium intake increases steady state messenger RNA levels of the type 1 angiotensin II receptor in the aorta and mesenteric resistance arteries, and that this increase is mediated by suppression of production of angiotensin II induced by a high sodium intake; and to test the hypotheses that angiotensin II administered at a pressor dose increases steady state messenger RNA levels of the angiotensin II type 1 receptor in the aorta and mesenteric resistance arteries, and that this increase is mediated by activation of angiotensin II type 1 receptors in these vessels.
In experiment 1, male Wistar rats were divided into four groups and treated for 2 weeks with a (0.5%) normal sodium diet, a normal-sodium diet plus angiotensin II, a high (4%) sodium diet, or a high-sodium plus angiotensin II. We infused 25 ng/kg per min angiotensin II subcutaneously by using osmotic pumps. In experiment 2, male Wistar rats were divided into four groups and treated for 2 weeks with vehicle, 1 mg/kg per day losartan by oral gavage, 250 ng/kg per min angiotensin II by using an osmotic pump), and losartan plus angiotensin II. Angiotensin II type 1 messenger mRNA was measured with the use of quantitative reverse transcriptase-polymerase chain reaction in the presence of an angiotensin II type 1 receptor mutant complementary RNA as internal standard.
Results from experiment 1 show that body weight and systolic tail-cuff blood pressures did not differ among our four groups (P > 0.05). Angiotensin II type 1 messenger RNA levels of rats in high-salt diet group were 73% (aorta) and 171% (mesenteric resistance arteries) greater than those of rats in normal-salt diet group (P < 0.05). In contrast, angiotensin II type 1 messenger RNA levels both in aorta and in mesenteric resistance arteries of rats in normal-salt diet plus angiotensin II and high-salt diet plus angiotensin II groups did not differ from those of rats in normal-salt diet group. Results from experiment 2 show that systolic blood pressures in rats treated with angiotensin II and with losartan plus angiotensin II were higher than those in rats administered vehicle (P < 0.05). Mean response of arterial pressure to bolus injection of angiotensin II was suppressed in losartan-treated rats compared with that in rats administered vehicle and in rats treated with losartan plus angiotensin II compared with that in rats treated with angiotensin II (P < 0.05). Angiotensin II type 1 messenger RNA levels were higher by 73% (in aorta) and 63% (in mesenteric resistance arteries) in rats treated with angiotensin II than they were in rats administered vehicle (P < 0.05), but not in both aorta and mesenteric resistance arteries in rats treated with losartan and losartan plus angiotensin II versus rats administered vehicle.
A high-salt diet increases angiotensin II type 1 messenger RNA levels both in aorta and in mesenteric resistance arteries. This increase is completely suppressed by simultaneous nonpressor infusion of angiotensin II, suggesting that angiotensin II negatively regulates vascular angiotensin II type 1 messenger RNA in normotensive rats. Hypertension induced by pressor infusion of angiotensin II increases angiotensin II type 1 messenger RNA levels both in aorta and in mesenteric resistance arteries. This increase can be prevented by administration of losartan at a nondepressor dose, suggesting that angiotensin II positively regulates vascular angiotensin II type 1 messenger RNA via activation of the angiotensin II type 1 receptor during hypertension.
验证以下假说，即高钠摄入会增加主动脉和肠系膜阻力动脉中1型血管紧张素II受体的稳态信使核糖核酸（mRNA）水平，且这种增加是由高钠摄入抑制血管紧张素II的生成所介导的；并验证以下假说，即给予升压剂量的血管紧张素II会增加主动脉和肠系膜阻力动脉中1型血管紧张素II受体的稳态mRNA水平，且这种增加是由这些血管中1型血管紧张素II受体的激活所介导的。
在实验1中，将雄性Wistar大鼠分为四组，分别用（0.5%）正常钠饮食、正常钠饮食加血管紧张素II、高（4%）钠饮食或高钠加血管紧张素II处理2周。我们使用渗透泵以每分钟25 ng/kg的剂量皮下输注血管紧张素II。在实验2中，将雄性Wistar大鼠分为四组，分别用赋形剂、每天1 mg/kg氯沙坦经口灌胃、使用渗透泵以每分钟250 ng/kg的剂量输注血管紧张素II以及氯沙坦加血管紧张素II处理2周。在存在1型血管紧张素II受体突变互补RNA作为内标的情况下，使用定量逆转录 - 聚合酶链反应测量1型血管紧张素II信使mRNA。
实验1的结果表明，四组大鼠的体重和收缩期尾袖血压无差异（P>0.05）。高盐饮食组大鼠的1型血管紧张素II信使mRNA水平比正常盐饮食组大鼠高73%（主动脉）和171%（肠系膜阻力动脉）（P<0.05）。相比之下，正常盐饮食加血管紧张素II组和高盐饮食加血管紧张素II组大鼠的主动脉和肠系膜阻力动脉中的1型血管紧张素II信使mRNA水平与正常盐饮食组大鼠无差异。实验2的结果表明，用血管紧张素II以及氯沙坦加血管紧张素II处理的大鼠的收缩压高于用赋形剂处理的大鼠（P<0.05）。与用赋形剂处理的大鼠相比，氯沙坦处理的大鼠对推注血管紧张素II的平均动脉压反应受到抑制；与用血管紧张素II处理的大鼠相比，氯沙坦加血管紧张素II处理的大鼠对推注血管紧张素II的平均动脉压反应受到抑制（P<0.05）。用血管紧张素II处理的大鼠的1型血管紧张素II信使mRNA水平比用赋形剂处理的大鼠高73%（主动脉）和63%（肠系膜阻力动脉）（P<0.05），但氯沙坦处理组和氯沙坦加血管紧张素II处理组大鼠的主动脉和肠系膜阻力动脉中的1型血管紧张素II信使mRNA水平与用赋形剂处理的大鼠相比无差异。
高盐饮食会增加主动脉和肠系膜阻力动脉中1型血管紧张素II信使mRNA水平。同时非升压输注血管紧张素II可完全抑制这种增加，这表明在正常血压大鼠中血管紧张素II对血管1型血管紧张素II信使mRNA起负调节作用。升压输注血管紧张素II诱导的高血压会增加主动脉和肠系膜阻力动脉中1型血管紧张素II信使mRNA水平。给予非降压剂量的氯沙坦可预防这种增加，这表明在高血压期间血管紧张素II通过激活1型血管紧张素II受体对血管1型血管紧张素II信使mRNA起正调节作用。
