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      Science Review: Vasopressin and the cardiovascular system part 2 – clinical physiology

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          Abstract

          Vasopressin is emerging as a rational therapy for vasodilatory shock states. In part 1 of the review we discussed the structure and function of the various vasopressin receptors. In part 2 we discuss vascular smooth muscle contraction pathways with an emphasis on the effects of vasopressin on ATP-sensitive K + channels, nitric oxide pathways, and interaction with adrenergic agents. We explore the complex and contradictory studies of vasopressin on cardiac inotropy and coronary vascular tone. Finally, we summarize the clinical studies of vasopressin in shock states, which to date have been relatively small and have focused on physiologic outcomes. Because of potential adverse effects of vasopressin, clinical use of vasopressin in vasodilatory shock should await a randomized controlled trial of the effect of vasopressin's effect on outcomes such as organ failure and mortality.

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          Most cited references94

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          The pathogenesis of vasodilatory shock.

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            Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle.

            Nitric oxide is the major endothelium-derived relaxing factor (EDRF), and it is thought to relax smooth muscle cells by stimulation of guanylate cyclase, accumulation of its product cyclic GMP, and cGMP-dependent modification of several intracellular processes, including activation of potassium channels through cGMP-dependent protein kinase. Here we present evidence that both exogenous nitric oxide and native EDRF can directly activate single Ca(2+)-dependent K+ channels (K+Ca) in cell-free membrane patches without requiring cGMP. Under conditions when guanylate cyclase was inhibited by methylene blue, considerable relaxation of rabbit aorta to nitric oxide persisted which was blocked by charybdotoxin, a specific inhibitor of K+Ca channels. These studies demonstrate a novel direct action of nitric oxide on K+Ca channels.
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              Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase.

              Nitric oxide (NO)-induced relaxation is associated with increased levels of cGMP in vascular smooth muscle cells. However, the mechanism by which cGMP causes relaxation is unknown. This study tested the hypothesis that activation of Ca-sensitive K (KCa) channels, mediated by a cGMP-dependent protein kinase, is responsible for the relaxation occurring in response to cGMP. In rat pulmonary artery rings, cGMP-dependent, but not cGMP-independent, relaxation was inhibited by tetraethylammonium, a classical K-channel blocker, and charybdotoxin, an inhibitor of KCa channels. Increasing extracellular K concentration also inhibited cGMP-dependent relaxation, without reducing vascular smooth muscle cGMP levels. In whole-cell patch-clamp experiments, NO and cGMP increased whole-cell K current by activating KCa channels. This effect was mimicked by intracellular administration of (Sp)-guanosine cyclic 3',5'-phosphorothioate, a preferential cGMP-dependent protein kinase activator. Okadaic acid, a phosphatase inhibitor, enhanced whole-cell K current, consistent with an important role for channel phosphorylation in the activation of NO-responsive KCa channels. Thus NO and cGMP relax vascular smooth muscle by a cGMP-dependent protein kinase-dependent activation of K channels. This suggests that the final common pathway shared by NO and the nitrovasodilators is cGMP-dependent K-channel activation.
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                Author and article information

                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                2004
                26 June 2003
                : 8
                : 1
                : 15-23
                Affiliations
                [1 ]Staff intensivist, Department of Medicine, Division of Critical Care, Kelowna General Hospital, Kelowna BC, Canada
                [2 ]Associate Professor, Department of Medicine, Columbia University, New York, New York, USA
                [3 ]Assistant Professor of Medicine, Faculty of Medicine, and Program Director, Critical Care Medicine, University of Toronto, and Consultant in Pulmonary and Critical Care Medicine, Director Pulmonary Hypertension Program, University Health Network, Toronto, Ontario, Canada
                Article
                cc2338
                10.1186/cc2338
                420051
                14975041
                55afe058-afd4-4c60-9b0f-982e22ae9425
                Copyright © 2004 BioMed Central Ltd
                History
                Categories
                Review

                Emergency medicine & Trauma
                oxytocin,nitric oxide,vasopressin,physiology,potassium channels,receptors,cardiac inotropy,vasoconstriction,hypotension,adrenergic agents,vascular,antidiurectic hormone,vasodilation,septic shock,smooth muscle

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