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.