Supowit S C, Zhao H, Hallman D M, DiPette D J
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555-1065, USA.
Hypertension. 1998 Jan;31(1 Pt 2):391-6. doi: 10.1161/01.hyp.31.1.391.
We previously demonstrated that the neuronal expression of calcitonin gene-related peptide (CGRP), a potent vasodilator, is increased in deoxycorticosterone-salt-induced hypertension where it acts as a compensatory vasodilator to attenuate the elevated blood pressure. To determine whether CGRP is playing a similar role in subtotal nephrectomy-salt-induced hypertension, hypertension was induced in Sprague-Dawley rats (n=6) by subtotal nephrectomy and 1.0% saline drinking water. Control rats (n=6) were sham operated and given tap water to drink. CGRP(8-37), a CGRP receptor antagonist, was used to assess the hemodynamic role of CGRP in this setting. CGRP mRNA and peptide levels in dorsal root ganglia were also determined. Three weeks after either protocol, all rats had intravenous (for drug administration) and arterial (for continuous mean arterial pressure monitoring) catheters surgically placed and were studied in the conscious, unrestrained state. CGRP(8-37) (3.2 or 6.4 x 10(4) pmol/L in 0.1 mL saline) and vehicle were administered intravenously to all rats. Baseline mean arterial pressure was higher in the subtotal nephrectomized rats compared with the controls (173+/-5 versus 113+/-5 mm Hg, P<.001). Vehicle administration did not change mean arterial pressure in either group, and CGRP(8-37) administration did not alter mean arterial pressure in the normotensive group. In contrast, CGRP(8-37) administration to the subtotal nephrectomized rats rapidly increased the already elevated mean arterial pressure at both the 3.2 x 10(4) pmol/L dose (7.8+/-1.1 mm Hg, P<.05) and the 6.4 x 10(4) pmol/L dose (9.6+/-0.8 mm Hg, P<.01). CGRP mRNA and peptide levels in the dorsal root ganglia were not significantly different between the two groups. These data suggest that in subtotal nephrectomy-salt-induced hypertension, CGRP may play a compensatory depressor role in an attempt to lower the elevated blood pressure.
我们先前证明，降钙素基因相关肽（CGRP，一种强效血管舒张剂）的神经元表达在脱氧皮质酮盐诱导的高血压中增加，在该高血压中它作为一种代偿性血管舒张剂来减轻血压升高。为了确定CGRP在肾次全切除盐诱导的高血压中是否发挥类似作用，通过肾次全切除术和给予1.0%盐水饮用水在Sprague-Dawley大鼠（n = 6）中诱导高血压。对照大鼠（n = 6）进行假手术并给予自来水饮用。使用CGRP受体拮抗剂CGRP(8 - 37)来评估CGRP在此情况下的血流动力学作用。还测定了背根神经节中的CGRP mRNA和肽水平。在任一方案实施三周后，所有大鼠均通过手术放置静脉导管（用于给药）和动脉导管（用于持续监测平均动脉压），并在清醒、不受约束的状态下进行研究。向所有大鼠静脉注射CGRP(8 - 37)（在0.1 mL盐水中为3.2或6.4×10⁴ pmol/L）和赋形剂。肾次全切除大鼠的基线平均动脉压高于对照组（173±5对113±5 mmHg，P <.001）。给予赋形剂在两组中均未改变平均动脉压，给予CGRP(8 - 37)在正常血压组中也未改变平均动脉压。相反，向肾次全切除大鼠给予CGRP(8 - 37)在3.2×10⁴ pmol/L剂量（7.8±1.1 mmHg，P <.05）和6.4×10⁴ pmol/L剂量（9.6±0.8 mmHg，P <.01）时均迅速升高了已升高的平均动脉压。两组背根神经节中的CGRP mRNA和肽水平无显著差异。这些数据表明，在肾次全切除盐诱导的高血压中，CGRP可能发挥代偿性降压作用以试图降低升高的血压。
