Zaidi M, Bevis P J
Department of Cellular and Molecular Sciences, St George's Hospital Medical School, London, United Kingdom.
Cardiovasc Res. 1991 Feb;25(2):125-8. doi: 10.1093/cvr/25.2.125.
Calcitonin gene related peptide (CGRP) is a potent endogenous vasodilator. The peptide is released from perivascular nerve endings and can normally be detected in the circulation. An attempt was made to determine the concentrations and partially characterise the immunoreactive forms of circulating CGRP in a genetically hypertensive rat strain, the "spontaneously hypertensive rat" (SHR) and its genetic control, Wistar-Kyoto (WKY).
Immunoreactive plasma CGRP levels were measured using a highly sensitive carboxyl terminal specific CGRP radioimmunoassay together with high performance liquid chromatography. Plasma immunoreactive CGRP (i-CGRP) levels were also measured 6 h after intraperitoneal colchicine administration (10 mg.kg-1 body weight) to both groups of rats.
Eight SHR rats were compared with eight WKY rats, both groups aged 7 weeks.
Mean i-CGRP levels were threefold higher in the SHR group compared to controls, while plasma calcitonin levels were not different between the two groups. There was a significant correlation (Kendall's correlation coefficient, r = 0.57; p = 0.024) between i-CGRP levels and the mean systolic blood pressure (measured by the indirect tail cuff method) in SHR but not WKY rats. Similar profiles of i-CGRP were observed in both SHR and WKY rats, when acid-methanol extracts of pooled plasma were chromatographed under similar conditions. It was also confirmed that circulating CGRP in both SHR and WKY strains was derived from perivascular nerve endings, by demonstrating a complete abolition from plasma of previously detectable i-CGRP following the administration of colchicine.
The study shows that CGRP is normally released from vascular nerve endings, and that high concentrations of the circulating peptide are found in hypertension. This might represent a mechanism to counteract the excessive vasoconstrictor influences that underly the development and maintenance of hypertension.
降钙素基因相关肽（CGRP）是一种强效的内源性血管舒张剂。该肽从血管周围神经末梢释放，通常可在循环系统中检测到。本研究旨在测定遗传性高血压大鼠品系“自发性高血压大鼠”（SHR）及其基因对照Wistar-Kyoto（WKY）中循环CGRP的浓度，并对其免疫反应形式进行部分表征。
使用高灵敏度的羧基末端特异性CGRP放射免疫分析法和高效液相色谱法测量免疫反应性血浆CGRP水平。对两组大鼠腹腔注射秋水仙碱（10mg·kg-1体重）6小时后，也测量了血浆免疫反应性CGRP（i-CGRP）水平。
将8只7周龄的SHR大鼠与8只WKY大鼠进行比较。
与对照组相比，SHR组的平均i-CGRP水平高出三倍，而两组之间的血浆降钙素水平没有差异。在SHR大鼠中，i-CGRP水平与平均收缩压（通过间接尾袖法测量）之间存在显著相关性（肯德尔相关系数，r = 0.57；p = 0.024），而在WKY大鼠中则没有。当在相似条件下对混合血浆的酸-甲醇提取物进行色谱分析时，在SHR和WKY大鼠中观察到相似的i-CGRP谱。通过证明给予秋水仙碱后血浆中先前可检测到的i-CGRP完全消失，还证实了SHR和WKY品系中的循环CGRP均来自血管周围神经末梢。
该研究表明，CGRP通常从血管神经末梢释放，并且在高血压患者中发现循环肽的浓度较高。这可能代表了一种抵消导致高血压发生和维持基础的过度血管收缩影响的机制。
