The role of calmodulin in neurotransmitter release and vascular responsiveness in spontaneously hypertensive rats.

This study was designed to investigate the role of calmodulin in adrenergic transmission in hypertension. In perfused mesenteric vasculature from spontaneously hypertensive rats (SHR, 7-9 weeks of age) and age-matched Wistar Kyoto rats (WKY), the effects of a specific calmodulin antagonist (W-7) on norepinephrine overflow and vascular responsiveness to endogenous and exogenous norepinephrine were examined. The vasoconstrictor responses to electrical nerve stimulation and exogenous norepinephrine as well as norepinephrine overflow during electrical nerve stimulation were significantly enhanced in SHR compared with those in age-matched WKY. The calmodulin antagonist, W-7, reduced not only vasoconstrictor responses but also norepinephrine overflow during nerve stimulation. These inhibitory effects of W-7 were significantly greater in SHR than in WKY. The results demonstrate that norepinephrine overflow from the sympathetic nerve endings and vascular responsiveness were increased in SHR. The marked reduction in norepinephrine overflow and pressor responses by W-7 might suggest the greater calmodulin-dependent adrenergic transmission in this model of hypertension.