Effects of a protein kinase C inhibitor (H-7) on norepinephrine release from vascular adrenergic neurons in spontaneously hypertensive rats.
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.
Tsuda
K
K
Department of Medicine, Wakayama Medical College, Japan.
Masuyama
Y
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000294:innervation*; D004558:Electric Stimulation; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013152:Splanchnic Circulation; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism*
D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D009638:Norepinephrine