Stewen Pia, Mervaala Eero, Karppanen Heikki, Nyman Tuulikki, Saijonmaa Outi, Tikkanen Ilkka, Fyhrquist Frej
Minerva Institute for Medical Research, Helsinki, Finland.
Hypertens Res. 2003 Jul;26(7):583-9. doi: 10.1291/hypres.26.583.
The regulation of both angiotensin receptors and bradykinin receptors during sodium intake is poorly understood. We hypothesized that an altered balance between renal angiotensin type 1 (AT1) receptors and bradykinin type 2 (B2) receptors might contribute to an increase in blood pressure during periods of high-sodium intake. We studied the effects of high-sodium intake on renal AT1 receptors and B2 receptors in 5-6-week-old spontaneously hypertensive rats (SHR) receiving high-sodium chloride (6% NaCl) or mineral salts (10.5%, composition: 57% NaCl, 28% KCl, 12% MgSO4) compared to those receiving a low-sodium (NaCl 0.125%) diet for 10 weeks. Mineral salt intake was included due to its beneficial effects on blood pressure and cardiac hypertrophy. Receptor densities were measured by quantitative autoradiography. AT1 receptors were quantified using incubation with 125I-Sar1-Ile8-angiotensin II and displacement was measured with PD123319 (10 micromol/l), whereas B2 receptors were quantified using 125I-HPP-icatibant and displacement was measured with icatibant (3 micromol/l). Compared to the SHR controls, a further increase in blood pressure occurred after 2 weeks in the 6% NaCl group and after 6 weeks in the mineral salt group. AT1 receptor density increased in the renal cortex by 41% (p<0.01) in the 6% NaCl group and by 26% (p<0.05) in the mineral salt group. B2 receptor density decreased in the renal medulla by 26% (p<0.01) in the 6% NaCl group, and decreased even more i.e., by 45% (p<0.001), in the mineral salt group. It was shown that a 6% NaCl or a 10.5% mineral salt loading was capable of increasing renal AT1 receptor density and decreasing renal B2 receptor density. An altered balance between these receptors might be associated with hypertension under conditions of sodium loading.
目前对钠摄入过程中血管紧张素受体和缓激肽受体的调节了解甚少。我们推测，肾血管紧张素1型（AT1）受体和缓激肽2型（B2）受体之间平衡的改变可能导致高钠摄入期间血压升高。我们研究了高钠摄入对5至6周龄自发性高血压大鼠（SHR）肾AT1受体和B2受体的影响，这些大鼠分别接受高氯化钠（6% NaCl）或矿物盐（10.5%，组成：57% NaCl，28% KCl，12% MgSO4），并与接受低钠（0.125% NaCl）饮食10周的大鼠进行比较。纳入矿物盐摄入是因为其对血压和心脏肥大有有益作用。通过定量放射自显影法测量受体密度。使用125I-Sar1-Ile8-血管紧张素II孵育来定量AT1受体，并用PD123319（10微摩尔/升）测量置换情况，而使用125I-HPP-icatibant定量B2受体，并用icatibant（3微摩尔/升）测量置换情况。与SHR对照组相比，6% NaCl组在2周后血压进一步升高，矿物盐组在6周后血压进一步升高。6% NaCl组肾皮质中AT1受体密度增加41%（p<0.01），矿物盐组增加26%（p<0.05）。6% NaCl组肾髓质中B2受体密度降低26%（p<0.01），矿物盐组降低更多，即降低45%（p<0.001）。结果表明，6% NaCl或10.5%矿物盐负荷能够增加肾AT1受体密度并降低肾B2受体密度。在钠负荷条件下，这些受体之间平衡的改变可能与高血压有关。
