Protein kinase C-dependent and calmodulin-dependent regulation of neurotransmitter release and vascular responsiveness in spontaneously hypertensive rats.
This study was designed to investigate the role of protein kinase C and calmodulin in adrenergic transmission in hypertension. In isolated mesenteric vasculature prepared from spontaneously hypertensive rats (SHR, Okamoto and Aoki strain) and age-matched Wistar-Kyoto rats (WKY), we examined the effects of protein kinase C inhibitor (H-7) and calmodulin antagonist (W-7) on pressor responses and noradrenaline release from the vascular adrenergic neurons. Endogenous noradrenaline release and vasoconstrictor responses evoked by periarterial nerve stimulation were significantly enhanced in SHR compared to those in age-matched WKY. Protein kinase C inhibitor H-7 and the calmodulin antagonist W-7 inhibited the stimulation-evoked noradrenaline release and pressor responses, respectively, in a dose-dependent manner. Further, these inhibitory effects of H-7 and W-7 were greater in SHR than in WKY. These results demonstrate that noradrenaline release and vascular responsiveness are increased in the mesenteric vasculatures of SHR. The marked reduction in noradrenaline release and pressor responses induced by H-7 and W-7 in SHR suggests the presence of enhanced protein kinase C-dependent and calmodulin-dependent regulation of adrenergic neurotransmission, which may contribute to the calcium abnormalities in this model of hypertension.
Tsuda
K
K
Department of Medicine, Wakayama Medical College, Japan.
Shima
H
H
Ura
M
M
Takeda
J
J
Kimura
K
K
Nishio
I
I
Masuyama
Y
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000503:physiopathology*; D002147:Calmodulin / Q000502:physiology*; D004558:Electric Stimulation; D006973:Hypertension / Q000503:physiopathology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008643:Mesentery / Q000098:blood supply / Q000294:innervation; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D009638:Norepinephrine