抗高血压药西氯他宁对自发性高血压大鼠肠系膜动脉灌注中去甲肾上腺素释放和血管收缩的影响。

Effects of the antihypertensive agent, cicletanine, on noradrenaline release and vasoconstriction in perfused mesenteric artery of SHR.

作者信息

Nasa Y, Yoshida H, Urata M, Uchibayashi K, Tsunoda Y, Kamigata K, Takeo S

机构信息

Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.

出版信息

Br J Pharmacol. 1998 Feb;123(3):427-34. doi: 10.1038/sj.bjp.0701622.

DOI:10.1038/sj.bjp.0701622

PMID:9504383

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565183/

Abstract

The mechanism by which cicletanine (CIC) exerts its antihypertensive effects has not been fully elucidated. The present study was undertaken to examine the effects of in vivo and in vitro treatment with CIC on the pressor response and noradrenaline (NA) overflow during periarterial nerve stimulation (PNS) in perfused mesenteric arterial beds isolated from spontaneously hypertensive rats (SHR). 2. CIC at a dose of 50 mg kg(-1) day(-1) was administered orally to both SHR and normotensive Wistar-Kyoto rats (WKY) from the 6th to 10th week of age. At the 10th week, the isolated mesenteric arterial bed was perfused with Krebs-Henseleit buffer and changes in perfusion pressure and NA overflow during PNS were measured. 3. Chronic treatment with CIC suppressed the age-related elevation of systemic blood pressure in SHR but not in WKY. 4. The PNS (20 Hz)-induced mesenteric vasoconstrictor response and NA overflow were greater in SHR than in WKY. In the vasculature of SHR chronic treatment with CIC resulted in a significant attenuation of the vasoconstriction and the NA overflow during PNS, whereas it did not alter vasoconstrictor responses to bolus injections of KCl and phenylephrine. 5. Treatment with 30 microM CIC in vitro diminished the PNS-induced vasoconstriction and NA overflow but not the NA- and KCl-induced vasoconstriction in the vasculature of untreated SHR. 6. In the vasculature of SHR PNS-induced NA overflow was attenuated by prostaglandin E2 (0.05 microM), whereas it was augmented by the cyclo-oxygenase inhibitor diclofenac-Na (30 microM). In the presence of diclofenac, in vitro treatment with CIC did not attenuate the NA overflow during PNS. 7. The results suggest that the antihypertensive effect of CIC in SHR is partially due to the presynaptic inhibition of NA release during sympathetic nerve activation. Transjunctional inhibition of NA release by prostaglandins may contribute to the inhibitory action of CIC on NA release in the vasculature of SHR.

摘要

西氯他宁（CIC）发挥其降压作用的机制尚未完全阐明。本研究旨在研究体内和体外给予CIC对从自发性高血压大鼠（SHR）分离的灌注肠系膜动脉床在动脉周围神经刺激（PNS）期间的升压反应和去甲肾上腺素（NA）溢出的影响。2. 从第6周龄至第10周龄，对SHR和正常血压的Wistar-Kyoto大鼠（WKY）口服给予剂量为50 mg kg⁻¹天⁻¹的CIC。在第10周时，用Krebs-Henseleit缓冲液灌注分离的肠系膜动脉床，并测量PNS期间灌注压力和NA溢出的变化。3. CIC的慢性治疗抑制了SHR中与年龄相关的全身血压升高，但对WKY没有影响。4. PNS（20 Hz）诱导的肠系膜血管收缩反应和NA溢出在SHR中比在WKY中更大。在SHR的血管系统中，CIC的慢性治疗导致PNS期间血管收缩和NA溢出显著减弱，而它并未改变对氯化钾和去氧肾上腺素推注的血管收缩反应。5. 在体外，用30 μM CIC处理可减少PNS诱导的血管收缩和NA溢出，但不会减少未处理SHR血管系统中NA和氯化钾诱导的血管收缩。6. 在SHR的血管系统中，PNS诱导的NA溢出被前列腺素E2（0.05 μM）减弱，而被环氧化酶抑制剂双氯芬酸钠（30 μM）增强。在双氯芬酸存在的情况下，体外给予CIC不会减弱PNS期间的NA溢出。7. 结果表明，CIC对SHR的降压作用部分归因于交感神经激活期间NA释放的突触前抑制。前列腺素对NA释放的跨接点抑制可能有助于CIC对SHR血管系统中NA释放的抑制作用。