Greater calmodulin-dependent regulation of neurotransmitter release and vascular responsiveness in chronic Doca-salt...

The present study was carried out to investigate the role of calmodulin in the adrenergic transmission of deoxycorticosterone acetate (DOCA)-salt hypertension. In perfused mesenteric vasculatures prepared from DOCA-salt hypertensive rats (seven to eight weeks after operation) and age-matched normotensive control rats, the effects of a specific calmodulin antagonist (W-7: N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide) on the norepinephrine release and vascular responsiveness were examined. Endogenous norepinephrine overflow during electrical nerve stimulation was significantly greater in the mesenteric vasculatures of DOCA-salt hypertensive rats both at low (5 Hz) and high (15 Hz) frequencies than in those of the normotensive controls. Vasoconstrictor responses to electrical nerve stimulation or exogenous norepinephrine were also enhanced in the DOCA-salt hypertension compared to those in the controls. The calmodulin antagonist (W-7) inhibited the stimulation-evoked norepinephrine overflow and pressor responses in a dose-dependent manner. The suppressive magnitudes in these responses by W-7 were significantly greater in the mesenteric vasculatures of the DOCA-salt hypertension than in those of the control rats. These results demonstrate that the vascular adrenergic neurotransmission might be enhanced in the mesenteric vasculatures of the DOCA-salt hypertensive rats. Further, it is suggested that the marked reduction in stimulation-evoked norepinephrine overflow and vasoconstrictor responses by W-7 showed the greater calmodulin-dependent regulation in the vascular adrenergic activity of DOCA-salt hypertension.