Tsuda K, Masuyama Y
Department of Medicine, Wakayama Medical College, Japan.
Clin Exp Hypertens A. 1990;12(4):581-96. doi: 10.3109/10641969009073486.
This study was performed to investigate the effects of a specific protein kinase C inhibitor (H-7) on vascular adrenergic transmission in hypertension. In the isolated mesenteric vasculature of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY), we have examined the effects of H-7 on norepinephrine (NE) release from vascular adrenergic neurons. Endogenous NE release during periarterial nerve stimulation was inhibited by H-7 in a dose-dependent manner with a concomitant reduction of pressor responses of the preparation. The inhibition of NE release was not affected by an uptake blocker of NE (desipramine). In SHR, the stimulation-evoked NE release and pressor responses were significantly greater than in age-matched WKY. The suppressive magnitude of stimulation-evoked NE release and pressor responses by H-7 were pronounced in SHR compared with WKY. These results demonstrate that endogenous NE release and pressor responses were increased in the mesenteric vasculature of SHR. Furthermore, the marked inhibition of NE release and pressor responses by H-7 in SHR may suggest the presence of enhanced protein kinase C-dependent regulation of vascular adrenergic transmission, which may contribute to the calcium-related abnormalities in this form of hypertension.
本研究旨在探讨一种特定的蛋白激酶C抑制剂（H-7）对高血压血管肾上腺素能传递的影响。在自发性高血压大鼠（SHR）和Wistar Kyoto大鼠（WKY）的离体肠系膜血管系统中，我们研究了H-7对血管肾上腺素能神经元去甲肾上腺素（NE）释放的影响。动脉周围神经刺激期间内源性NE释放受到H-7的剂量依赖性抑制，同时制剂的升压反应降低。NE释放的抑制不受NE摄取阻滞剂（地昔帕明）的影响。在SHR中，刺激诱发的NE释放和升压反应显著大于年龄匹配的WKY。与WKY相比，H-7对SHR中刺激诱发的NE释放和升压反应的抑制程度更为明显。这些结果表明，SHR肠系膜血管系统中内源性NE释放和升压反应增加。此外，H-7对SHR中NE释放和升压反应的显著抑制可能表明存在增强的蛋白激酶C依赖性血管肾上腺素能传递调节，这可能导致这种高血压形式中与钙相关的异常。
