Kawasaki H, Takenaga M, Araki H, Futagami K, Gomita Y
Department of Clinical Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700, Japan.
J Pharmacol Exp Ther. 1998 Feb;284(2):508-15.
The role of angiotensin (Ang) in neurotransmission of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in perfused mesenteric vascular beds isolated from spontaneously hypertensive rats (SHR) (8- and 15-week-old) and age-matched Wistar Kyoto rats (WKY) was investigated. In both SHR and WKY preparations precontracted by continuous perfusion of Krebs' solution containing 7 microM methoxamine plus 5 microM guanethidine, periarterial nerve stimulation (PNS; 1 and 2 Hz) produced a frequency-dependent vasodilation, which was abolished by 100 nM tetrodotoxin and 500 nM CGRP(8-37) (CGRP receptor antagonist). The PNS-induced vasodilation in the SHR decreased with age and was smaller than that in the WKY. The neurogenic vasodilation in the SHR but not WKY was significantly inhibited by N-acetyltetradecapeptide renin substrate (RS, 100 and 500 nM), AngI (50 and 100 nM) and AngII (50 and 100 nM). The inhibitory effects of RS, AngI and AngII were abolished by the AngII receptor antagonist, [Sar1,Ile8]AngII (500 nM). The effect of RS and AngI was inhibited by captopril (5 microM) and temocapril (500 nM). AngII (100 nM) had no effect on vasodilator response to exogenously infused CGRP (100 pmol). PNS (2 Hz) of perfused mesenteric vascular beds increased the release of CGRP-like immunoreactivities (CGRP-LI) in the perfusate, which was less in 15-week-old SHR than in age-matched WKY. AngII (100 nM) significantly inhibited the neurogenic release of CGRP-LI in the SHR but not in the WKY. These results suggest that exogenous and locally converted AngII, via AngII receptors, modulates the neurotransmission of CGRP-containing vasodilator nerves by inhibiting CGRP release from the nerve.
研究了血管紧张素（Ang）在自发性高血压大鼠（SHR，8周龄和15周龄）和年龄匹配的Wistar Kyoto大鼠（WKY）分离的灌注肠系膜血管床中含降钙素基因相关肽（CGRP）的血管舒张神经神经传递中的作用。在通过连续灌注含7μM甲氧明加5μM胍乙啶的Krebs溶液预收缩的SHR和WKY制剂中，动脉周围神经刺激（PNS；1和2Hz）产生频率依赖性血管舒张，100nM河豚毒素和500nM CGRP（8-37）（CGRP受体拮抗剂）可消除这种血管舒张。SHR中PNS诱导的血管舒张随年龄降低，且小于WKY中的血管舒张。SHR而非WKY中的神经源性血管舒张受到N-乙酰十四肽肾素底物（RS，100和500nM）、AngI（50和100nM）和AngII（50和100nM）的显著抑制。RS、AngI和AngII的抑制作用被AngII受体拮抗剂[Sar1，Ile8]AngII（500nM）消除。RS和AngI的作用被卡托普利（5μM）和替莫卡普利（500nM）抑制。AngII（100nM）对外源性注入CGRP（100pmol）的血管舒张反应无影响。灌注肠系膜血管床的PNS（2Hz）增加了灌注液中CGRP样免疫反应性（CGRP-LI）的释放，15周龄SHR中的释放少于年龄匹配的WKY。AngII（100nM）显著抑制SHR中CGRP-LI的神经源性释放，但不抑制WKY中的释放。这些结果表明，外源性和局部转化产生的AngII通过AngII受体，通过抑制神经释放CGRP来调节含CGRP血管舒张神经的神经传递。
