Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental myocardial infarction is a model of cardiac overload in which part of the cardiac muscle is removed. The resulting left ventricle insufficiency depends on the size of the infarct and time. The infarcted area remodels, due to proteolytic activity of inflammatory cells and collagenogenesis from fibroblast activity. The phenotype of the residual healthy cardiac muscle undergoes modification, and there are peripheral vascular changes which are partly dependent on the activation of pressor systems and/or inactivation of dilator systems. The changes are proportional to the infarct size at any given time after induction of the model. The degree of right ventricular hypertrophy and the drop in arterial pressure are upstream and downstream markers of the loss of left ventricular function and therefore indicate the extent of the remodelling. The increase of type V3isomyosin, the amount of subendocardial collagen, and the biosynthesis, storage and secretion of atrial natriuretic factor (ANF) are all proportional to the infarct size and the degree of cardiac overload. The level of urinary cGMP is also correlated with infarct size. These indices show ventricular remodelling, increased stress and energy restriction of the residual healthy cardiac muscle. The activation of peripheral pressor systems also depends on infarct size. They reflect the influence of defective cardiac pumping on the kidney, liver, brain and endothelium. Massive infarcts are accompanied by an increase in circulating renin and in renal renin content, by a decrease in angiotensinogen due to its consumption by renin, and to its insufficient hepatic synthesis, and by an increase in vasopressin secretion and biosynthesis in the hypothalamus. Converting enzyme inhibition has beneficial effect in this model by lowering cardiac load. It reduces arterial pressure, reverses bi-atrial and right ventricular hypertrophy, reduces the changes in the myosin isoenzyme patterns, and normalizes subendocardial fibrosis and the level of ANF. Although the effects of converting enzyme inhibition are beneficial in this model, they are restricted by their inability to normalize the load and stress when the initial loss of cardiac contractile material exceeds 40%.
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PMID:Left ventricular remodelling following experimental myocardial infarction. 882 57

Terminal differentiation of myogenic cells has long been known to be positively regulated by insulin-like growth factors (IGFs). Arg8-vasopressin (AVP) has been recently reported to potently induce myogenic differentiation. In the present study, the effects and the mechanisms of action of AVP and IGFs on myogenic cells have been investigated under conditions allowing growth and differentiation of myogenic cells in a simple serum-free medium. Under these conditions, L6 and L5 myogenic cells slowly proliferate and do not undergo differentiation (less than 1% fusion up to 7 days). AVP rapidly (2-3 days) and dose-dependently induces the formation of multinucleated myotubes. Creatine kinase activity and myosin accumulation are strongly up-regulated by AVP. Insulin or IGF-I or IGF-II, at concentrations that cause extensive differentiation in serum-containing medium, induces a modest degree of differentiation in serum-free medium. The simultaneous presence of AVP and of one of the IGFs in the synthetic medium induces maximal differentiation of L6, L5, and satellite cells. The expression of both myogenin and Myf-5 is dramatically stimulated by AVP. Our results indicate that AVP induces a significant level of myogenic differentiation in the absence of other factors. Furthermore, they suggest that to express their full myogenic potential, IGFs require the presence of other factors normally present in serum and fully mimicked by AVP. These studies support the conclusion that terminal myogenic differentiation may depend on the presence of differentiation factors rather than the absence of growth factors.
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PMID:Vasopressin and insulin-like growth factors synergistically induce myogenesis in serum-free medium. 948 52

This study correlates whole organ measurements of intracellular calcium concentration ([Ca(2+)](i)) with hormone-induced (epinephrine, vasopressin) changes of liver functions (glucose release, K(+) balance and bile flow). [Ca(2+)](i) was measured in the isolated perfused rat liver using the sensor Fura-2 and applying liver surface fluorescence spectroscopy. The technique was improved by (i) minimizing biliary elimination of the sensor by employing a rat strain deficient in canalicular organic anion transport (TR(-) mutation) and (ii) by correcting for changes of interfering intrinsic organ fluorescence that was shown to depend on the oxidation-reduction state (NAD(P)H content) of the organ. Epinephrine (50 nM) elicits an instantaneous peak rise of [Ca(2+)](i) to approx. 400 nM, followed by a sustained elevation that depends on the presence of extracellular Ca(2+). The rise of [Ca(2+)](i) coincides with initiation of glucose release, transient K(+) uptake, and transient stimulation of bile flow. Vasopressin (2 nM) exerts qualitatively similar effects. The transient rise of bile flow is attributed to Ca(2+)-mediated contraction of the pericanalicular actin-myosin web of hepatocytes.
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PMID:Intracellular calcium in the isolated rat liver: correlation to glucose release, K(+) balance and bile flow. 1172 35

We have previously demonstrated that vasopressin increases the water permeability of the inner medullary collecting duct (IMCD) by inducing trafficking of aquaporin-2 to the apical plasma membrane and that this response is dependent on intracellular calcium mobilization and calmodulin activation. Here, we address the hypothesis that this water permeability response is mediated in part through activation of the calcium/calmodulin-dependent myosin light chain kinase (MLCK) and regulation of non-muscle myosin II. Immunoblotting and immunocytochemistry demonstrated the presence of MLCK, the myosin regulatory light chain (MLC), and the IIA and IIB isoforms of the non-muscle myosin heavy chain in rat IMCD cells. Two-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry identified two isoforms of MLC, both of which also exist in phosphorylated and non-phosphorylated forms. 32P incubation of the inner medulla followed by autoradiography of two-dimensional gels demonstrated increased 32P labeling of both isoforms in response to the V2 receptor agonist [deamino-Cys1,D-Arg8]vasopressin (DDAVP). Time course studies of MLC phosphorylation in IMCD suspensions (using immunoblotting with anti-phospho-MLC antibodies) showed that the increase in phosphorylation could be detected as early as 30 s after exposure to vasopressin. The MLCK inhibitor ML-7 blocked the DDAVP-induced MLC phosphorylation and substantially reduced [Arg8]vasopressin (AVP)-stimulated water permeability. AVP-induced MLC phosphorylation was associated with a rearrangement of actin filaments (Alexa Fluor 568-phalloidin) in primary cultures of IMCD cells. These results demonstrate that MLC phosphorylation by MLCK represents a downstream effect of AVP-activated calcium/calmodulin signaling in IMCD cells and point to a role for non-muscle myosin II in regulation of water permeability by vasopressin.
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PMID:Non-muscle myosin II and myosin light chain kinase are downstream targets for vasopressin signaling in the renal collecting duct. 1534 43

Epithelial cells rely on proper targeting of cellular components to perform their physiological function. This dynamic process utilizes the cytoskeleton and involves movement of vesicles to and from the plasma membrane, thus traversing the actin cortical cytoskeleton. Studies support both direct interaction of actin with channels and an indirect mechanism whereby actin may serve as a track in the final delivery of the channel to the plasma membrane. Actin-dependent processes are often mediated via a member of the myosin family of proteins. Myosin I family members have been implicated in multiple cellular events occurring at the plasma membrane. In these studies, we investigated the function of the unconventional myosin I Myo1c in the M1 mouse collecting duct cell line. Myo1c was observed to be concentrated at or near the plasma membrane, often in discrete membrane domains. To address the possible role of Myo1c in channel regulation, we expressed a truncated Myo1c, lacking ATP and actin domains, in M1 cells and compared electrophysiological responses to control M1 cells, M1 cells expressing the empty vector, and M1 cells expressing the full-length Myo1c construct. Interestingly, cells expressing the Myo1c constructs had modulated antidiuretic hormone (ADH)-stimulated short-circuit current and showed little inhibition of short-circuit current with amiloride addition. Evaluation of enhanced green fluorescent protein-Myo1c constructs supports the importance of the IQ region in targeting the Myo1c to its respective cellular domain. These data are consistent with Myo1c participating in the regulation of the Na+ channel after ADH stimulation.
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PMID:Expression of the unconventional myosin Myo1c alters sodium transport in M1 collecting duct cells. 1571 23

Arginine-vasopressin (AVP) regulates water reabsorption in renal collecting duct principal cells. Its binding to Gs-coupled vasopressin V2 receptors increases cyclic AMP (cAMP) and subsequently elicits the redistribution of the water channel aquaporin-2 (AQP2) from intracellular vesicles into the plasma membrane (AQP2 shuttle), thereby facilitating water reabsorption from primary urine. The AQP2 shuttle is a paradigm for cAMP-dependent exocytic processes. Using sections of rat kidney, the AQP2-expressing cell line CD8, and primary principal cells, we studied the role of the motor protein myosin Vb, its vesicular receptor Rab11, and the myosin Vb- and Rab11-binding protein Rab11-FIP2 in the AQP2 shuttle. Myosin Vb colocalized with AQP2 intracellularly in resting and at the plasma membrane in AVP-treated cells. Rab11 was found on AQP2-bearing vesicles. A dominant-negative myosin Vb tail construct and Rab11-FIP2 lacking the C2 domain (Rab11-FIP2-DeltaC2), which disrupt recycling, caused condensation of AQP2 in a Rab11-positive compartment and abolished the AQP2 shuttle. This effect was dependent on binding of myosin Vb tail and Rab11-FIP2-DeltaC2 to Rab11. In summary, we identified myosin Vb as a motor protein involved in AQP2 recycling and show that myosin Vb- and Rab11-FIP2-dependent recycling of AQP2 is an integral part of the AQP2 shuttle.
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PMID:A Role of myosin Vb and Rab11-FIP2 in the aquaporin-2 shuttle. 1715 9

While pharmaceutical innovation has been highly successful in reducing mortality in chronic heart failure, this has not been matched by similar success in decompensated heart failure syndromes. Despite outstanding issues over definitions and end points, we argue in this paper that an unprecedented wealth of pharmacologic innovation may soon transform the management of these challenging patients. Agents that target contractility, such as cardiac myosin activators and novel adenosine triphosphate-dependent transmembrane sodium-potassium pump inhibitors, provide inotropic support without arrhythmogenic increases in cytosolic calcium or side effects of more traditional agents. Adenosine receptor blockade may improve glomerular filtration and diuresis by exerting a direct beneficial effect on glomerular blood flow while vasopressin antagonists promote free water excretion without compromising renal function and may simultaneously inhibit myocardial remodeling. Urodilatin, the renally synthesized isoform of atrial natriuretic peptide, may improve pulmonary congestion via vasodilation and enhanced diuresis. Finally, metabolic modulators such as perhexiline may optimize myocardial energy utilization by shifting adenosine triphosphate production from free fatty acids to glucose, a unique and conceptually appealing approach to the management of heart failure. These advances allow optimism not only for the advancement of our understanding and management of decompensated heart failure syndromes but for the translational research effort in heart failure biology in general.
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PMID:Emerging therapies for the management of decompensated heart failure: from bench to bedside. 1717 76

Given the limitations of high-dose diuretics and vasodilators and the increasing literature showing that inotropes, regardless of the dose used, have a detrimental effect on mortality, a variety of new agents are under investigation for the treatment of pulmonary and systemic congestion and restoration of cardiac output in the setting of acute heart failure syndromes. The new therapeutic approach is based on two goals: short-term improvement in symptoms together with long-term improvement of cardiac function. This review describes new agents that are in preclinical and in clinical phases with realistic prospects: anti-endothelin, natriuretic peptides, istaroxime, levosimendan, myosin activators, and vasopressin antagonists. Those new therapeutic strategies aim to act at the cellular level to improve vessel and heart functions, with minimal side effects, together with improved sodium and water balance.
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PMID:New pharmacologic therapies for acute heart failure. 1815 70

In addition to its role in artery contraction, Rho kinase (ROCK) is reported to be involved in the Ca(2+) response to vasoconstrictor agonist in rat aorta. However the signaling pathway mediated by ROCK had not been investigated so far and it was not known whether ROCK also contributed to Ca(2+) signaling in cultured vascular smooth muscle cells (VSMC), which undergo profound phenotypic changes. Our results showed that in VSMC, ROCK inhibition by Y-27632 or H-1152 had no effect on the Ca(2+) response to vasopressin, while in aorta the vasopressin-induced Ca(2+) entry was significantly decreased. The inhibition of myosin light chain kinase (MLCK) by ML-7 depressed the vasopressin-induced Ca(2+) signal in aorta but not in VSMC. The difference in ROCK sensitivity of vasopressin-induced Ca(2+) entry between aorta and VSMC was not related to an alteration of the RhoA/ROCK pathway. However, MLCK expression and activity were depressed in cultured cells compared to aorta. We concluded that the regulation of vasopressin-induced Ca(2+) entry by ROCK in aorta could involve the myosin cytoskeleton and could be prevented by the downregulation of MLCK in VSMC. These results underline the important differences in Ca(2+) regulation between whole tissue and cultured cells.
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PMID:Rho kinase regulation of vasopressin-induced calcium entry in vascular smooth muscle cell: comparison between rat isolated aorta and cultured aortic cells. 2288 50

The pharmacological treatment of dilated cardiomyopathy overlaps with the treatment of heart failure. The primary objective of this treatment is to slow the progression of disease and improve quality and length of life. All patients, including those with asymptomatic dysfunction of the left ventricle, ought to receive angiotensin converting enzyme inhibitors, (in the case of intolerance, angiotensin receptor blockers), and beta blockers. The results of studies involving aliskiren have been, so far, disappointing. In symptomatic heart failure NYHA II-IV diuretics and mineralcorticoid receptor antagonists should be added to treatment. Digoxin is recommended in the event of atrial fibrillation, and otherwise only in the event of NYHA III and IV. Ivabradine is recommended for patients with sinus rhythm and pulse rate of > 70/min. In decompensation of heart failure, dobutamine, phosphodiesterase inhibitors or levosimendan are administered over the short-term. Of the recent treatment options, the vasopressin blocker and adenosine A1 receptor antagonist (rolofylline) were disappointing. One treatment with potential for the future is omecamtiv mecarbil, a heart myosin activator.
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PMID:Pharmacotherapy of dilated cardiomyopathy. 2548 45


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