Gao Y, Nishimura Y, Suzuki A, Yoshida K
Department of Pharmacology, Kinki University School of Medicine, Osaka, Japan.
J Smooth Muscle Res. 1994 Feb;30(1):9-19. doi: 10.1540/jsmr.30.9.
The relaxant effects of calcitonin gene-related peptide (CGRP) on the 3rd branches of renal arteries obtained from stroke-prone spontaneously hypertensive rats (SHRSP), and Wistar-Kyoto rats (WKY) were investigated in vitro. CGRP elicited concentration-dependent relaxation, and the relaxant response was not affected by the mechanical removal of endothelium in either SHRSP or WKY. The CGRP-induced relaxant response was markedly greater in SHRSP than in WKY, whereas there was no significant difference in acetylcholine-induced relaxation, which was endothelium-dependent, between the two groups. Additionally, significantly enhanced reactivity to CGRP was also shown in spontaneously hypertensive rats compared to WKY; however, this reactivity was less than that observed in SHRSP. There were also no significant differences between WKY and SHRSP in the relaxation induced by forskolin, dibutyryl cyclic AMP, and 3-isobutyl-1-methylxanthine (IBMX). CGRP-induced relaxation was significantly potentiated in similar manner by the pretreatment with IBMX in both WKY and SHRSP. Incubation with glibenclamide (10(-6) M) had no effect on CGRP-induced relaxation in either group, the WKY or the SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the small renal arteries in the rat, and that the increased CGRP-induced relaxant response found in SHRSP may not be associated with the altered vasodilation mediated by cyclic AMP, or with functional changes in ATP-sensitive potassium channels.
在体外研究了降钙素基因相关肽（CGRP）对易卒中型自发性高血压大鼠（SHRSP）和Wistar-Kyoto大鼠（WKY）肾动脉三级分支的舒张作用。CGRP引起浓度依赖性舒张，且在SHRSP或WKY中，机械去除内皮均不影响舒张反应。CGRP诱导的舒张反应在SHRSP中明显大于WKY，而两组之间乙酰胆碱诱导的依赖内皮的舒张反应无显著差异。此外，与WKY相比，自发性高血压大鼠对CGRP的反应性也显著增强；然而，这种反应性低于SHRSP中观察到的反应性。WKY和SHRSP在福司可林、二丁酰环磷腺苷和3-异丁基-1-甲基黄嘌呤（IBMX）诱导的舒张方面也无显著差异。在WKY和SHRSP中，用IBMX预处理均以类似方式显著增强了CGRP诱导的舒张。用格列本脲（10^(-6) M）孵育对两组（WKY或SHRSP）中CGRP诱导的舒张均无影响。这些结果表明，CGRP在大鼠小肾动脉中产生不依赖内皮的舒张，且在SHRSP中发现的CGRP诱导的舒张反应增强可能与环磷腺苷介导的血管舒张改变或ATP敏感性钾通道的功能变化无关。
