Effects of calmodulin antagonists on norepinephrine release and vascular responsiveness in rat mesenteric vasculature

This study was designed to investigate the role of calmodulin in adrenergic neurotransmission of resistance vessels. The effects of various calmodulin antagonists (trifluoperazine, W-7, calmidazolium, chlorpromazine, fluphenazine) on the vascular responsiveness and norepinephrine overflow from adrenergic nerve endings were examined in perfused rat mesenteric vasculature preparations. Pressor responses to electrical nerve stimulation or exogenous norepinephrine were inhibited dose-dependently by each calmodulin antagonist. Norepinephrine overflow from the sympathetic nerve endings during electrical nerve stimulation was also suppressed by calmodulin antagonists. These results indicate that calmodulin antagonists affected both pre- and post-synaptic sites of adrenergic neurotransmission, suggesting that calmodulin is involved both in neurosecretion and vascular smooth muscle contractions in peripheral resistance vessels.