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

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.
 ...
PMID:Vasopressin administration facilitates fluid removal during hemodialysis. 1750 85

Volume retention in heart failure, nephrotic syndrome, and liver cirrhosis reflects pathological changes in homeostatic mechanisms that regulate the extracellular volume (sympathetic activity, renin-angiotensin-aldosterone system [RAAS], natriuretic peptides) and plasma osmolality (antidiuretic hormone [ADH]). In heart failure and liver cirrhosis, these changes are induced by a reduction of the effective circulating volume, which is the part of the extracellular fluid that is within the arterial system and effectively perfusing the tissues. This reduction in the effective circulating volume is caused by reduced cardiac output (heart failure), or by splanchnic vasodilatation with arterial underfilling (liver cirrhosis). In both cases, baroreceptors in both the carotid sinuses and in the glomerular afferent arterioles upregulate RAAS- and sympathetic activity, resulting in systemic vasoconstriction and renal sodium (and volume) retention. More severe reductions in the effective circulating volume may additionally stimulate ADH release, thus increasing the reabsorption of free water with subsequent hyponatriemia. In nephrotic syndrome, volume retention results either directly from the primary renal disease, which induces renal sodium and volume retention ("overfilling"), or indirectly from the reduced plasma oncotic pressure due to hypoalbuminemia, which induces a fluid shift from the intravascular to the interstitial space ("underfilling") with subsequent acitivation of baroreceptors and secondary sodium and volume retention.
 ...
PMID:[Volume retention in heart failure, nephrotic syndrome, and liver cirrhosis]. 1700 41

Fluid, electrolyte and mineral perturbations are prevalent features of tropical disease. Hemodynamic alterations, fever, nitrogen wasting, and changes in membrane transport and acid-base balance contribute to these perturbations. Models of malaria and leptospirosis have been used to show that common hemodynamic changes in tropical disease include decreased systemic vascular resistance, increased cardiac output and increased renal vascular resistance. Blood volume is initially increased, but it decreases as disease progresses. Response to fluid loading is decreased. Diabetes insipidus is occasionally observed in malaria. Hyponatremia occurs frequently in tropical diseases, as a result of increased levels of antidiuretic hormone (vasopressin), entry of sodium into cells, sodium loss and resetting of osmoreceptors. Natriuresis and kaliuresis are observed in patients with leptospirosis. Large amounts of sodium and potassium are lost in stool as a result of diarrhea. Hypernatremia is uncommon, whereas hypokalemia caused by hyperventilation is often observed (more frequently in patients with leptospirosis and kaliuresis). During severe tropical infective episodes, hyperkalemia results from intravascular hemolysis or rhabdomyolysis, and occasionally from decreased activity of Na+,K+-ATPase. Hypocalcemia, hypomagnesemia and hypophosphatemia are common features of both malaria and leptospirosis. Loss of magnesium in the urine is uniquely associated with leptospiral nephropathy. Hypozincemia and hypocupremia can also develop during tropical infection, and might interfere with a patient's immune response. These electrolyte and mineral perturbations are transient and quickly resolve when the disease is controlled.
 ...
PMID:Altered fluid, electrolyte and mineral status in tropical disease, with an emphasis on malaria and leptospirosis. 1822 2

Autosomal dominant polycystic kidney disease, a leading cause of end-stage renal disease in adults, is characterized by progressive focal cyst formation in the kidney. Embryonic lethality of Pkd1-targeted mice limits the use of these mice. Here we developed a floxed allele of Pkd1 exons 2-6. Global deletion mutants developed polyhydramnios, hydrops fetalis, polycystic kidney and pancreatic disease. Somatic Pkd1 inactivation in the kidney was achieved by crossing Pkd1(flox) mice with transgenic mice expressing Cre controlled by a gamma-glutamyltranspeptidase promoter. These mutants developed cysts in both proximal and distal nephron segments and survived for about 4 weeks. Somatic loss of heterozygosity was shown in a reporter mouse strain to cause cystogenesis. Some cysts in young mice are positive for multiple tubular markers and a mesenchymal marker, suggesting a delay in tubular epithelial differentiation. A higher cell proliferation rate was observed in distal nephron segments probably accounting for the faster growth rate of distal cysts. Although we observed an overall increase in apoptosis in cystic kidneys, there was no difference between proximal or distal nephron segments. We also found increased cyclic AMP, aquaporin 2 and vasopressin type 2 receptor mRNA levels, and apical membrane translocation of aquaporin 2 in cystic kidneys, all of which may contribute to the differential cyst growth rate observed. The accelerated polycystic kidney phenotype of these mice provides an excellent model for studying molecular pathways of cystogenesis and to test therapeutic strategies.
 ...
PMID:A mouse model for polycystic kidney disease through a somatic in-frame deletion in the 5' end of Pkd1. 1838 65

The available treatment options for hyponatremia secondary to SIADH are limited and not completely effective. Conivaptan is a vasopressin 1a and 2 receptor antagonist recently approved by the US Food and Drug Administration (FDA) for treating euvolemic and hypervolemic hyponatremia in adult patients. However, data on efficacy and safety of conivaptan in pediatrics are limited. We report a case of a 13-year-old boy with extensively metastasized anaplastic large-cell lymphoma. He also developed hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) prior to chemotherapy initiation. SIADH management in this case was complicated when fluid restriction was not safely attainable. Conivaptan played a significant role in this situation by allowing provision of a large amount of intravenous fluid prior to and during induction chemotherapy. It proved to be an important component in preventing uric acid nephropathy/tumor lysis syndrome. Conivaptan induced free-water clearance as indicated by increased urine output and decreased urine osmolality. The patient responded to conivaptan without any adverse effects.
 ...
PMID:Use of conivaptan to allow aggressive hydration to prevent tumor lysis syndrome in a pediatric patient with large-cell lymphoma and SIADH. 1843 28

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders. It accounts for 6% of the incidence of end-stage renal disease in Europe. Over the last decade, knowledge of the pathology underlying this disease has increased rapidly. Attributing important roles to tubular cell ciliary functioning, cell proliferation and fluid secretion, subsequent alterations in levels of intracellular calcium, adenosine 3',5'-cyclic monophosphate (cAMP) and activation of a variety of cellular kinases, including mammalian target of rapamycin (mTOR), has laid out the foundations for development of potentially effective treatments. In this editorial, the possible therapeutic roles for vasopressin antagonists, rapamycin, somatostatin and roscovitine are discussed. Clinical trials have been started to investigate the efficacy and safety of these agents for treating ADPKD in humans.
 ...
PMID:Better understanding of ADPKD results in potential new treatment options: ready for the cure? 1844 6

Intradialytic hypotension likely results from hypovolemia as well as patient and dialysis-specific factors. An impaired vasoconstrictive response to volume loss during hemodialysis has been demonstrated and increasing evidence suggests that deficiency in the hormone arginine vasopressin may be a contributing factor. Although vasopressin is widely recognized for its role in the regulation of serum osmolality, vasopressin is also an important regulator of blood pressure in health and in various disease states. That vasopressin deficiency contributes to the pathogenesis of intradialytic hypotension is suggested by several observations. First, vasopressin levels typically fall during hemodialysis when a rise might be expected as a result of volume loss. Second, therapies that prevent a fall in osmolality during dialysis, including dialysis against a high sodium bath and isolated ultrafiltration, have been shown to improve intradialytic blood pressure stability. Finally, and perhaps most importantly, the administration of low-dose exogenous vasopressin during dialysis has been shown to support blood pressure and improve volume removal. Further research is needed to determine the effect of chronic vasopressin (or selective V1a agonist) administration during dialysis on volume removal, inter- and intradialytic blood pressure control, and, ultimately, clinical outcomes in end-stage renal disease patients on dialysis.
 ...
PMID:Endogenous and exogenous vasopressin during hemodialysis. 1952 59

Blockade of the renin-angiotensin system (RAS), the standard treatment for chronic proteinuric nephropathy, slows but may not halt progression of the disease, particularly when therapy is started late. Because vasopressin may also play a role in the progression of renal disease, we measured the effect of a dual V(1a) and V(2) vasopressin receptor antagonist (RWJ-676070) alone or combined with angiotensin-converting enzyme inhibition or angiotensin II type 1 receptor blockade on proteinuria and renal disease progression during overt nephropathy. Twenty-one days after renal mass reduction, a time of established injury, rats were given vehicle, RWJ-676070, enalapril, losartan, RWJ-676070 plus enalapril, or losartan in drinking water for an additional 39 days. RWJ-676070 returned the blood pressure to pre-treatment levels, which were significantly lower than those in vehicle-treated rats. Enalapril, losartan, and the combined therapies reduced blood pressure to a greater extent. RWJ-676070 afforded a partial antiproteinuric effect, which was enhanced by the addition of enalapril or losartan. Renal functional impairment, and glomerular and tubular changes were partially ameliorated by RWJ-676070; parameters significantly improved with either enalapril or losartan alone and improved to a greater extent with the combined therapies. Our findings suggest that vasopressin receptor antagonists could be of additional therapeutic value in the treatment of chronic proteinuric nephropathy.
 ...
PMID:V1/V2 Vasopressin receptor antagonism potentiates the renoprotection of renin-angiotensin system inhibition in rats with renal mass reduction. 1982 11

Stimulus-secretion coupling (SSC) in endocrine cells remains underappreciated as a subject for the study/teaching of general physiology. In the present article, we review key new electrophysiological, electrochemical, and fluorescence optical techniques for the study of exocytosis in single cells that have made this a fertile area for recent research. Based on findings using these techniques, we developed a model of SSC for adrenal chromaffin cells that blends features of Ca(2+) entry-dependent SSC (characteristic of neurons) with G protein receptor-coupled, Ca(2+) release-dependent, and second messenger-dependent SSC (characteristic of epithelial exocrine cells and nucleated blood cells). This model requires two distinct pools of secretory graunules with differing Ca(2+) sensitivities. We extended this model to account for SSC in a wide variety of peripheral and hypothalamic/pituitary-based endocrine cells. These include osmosensitive magnocellular neurosecretory cells releasing antidiuretic hormone, stretch-sensitive atrial myocytes secreting atrial natriuretic peptide, K(+)-sensitive adrenal glomerulosa cells secreting aldosterone, Ca(2+)-sensitive parathyroid chief cells secreting parathyroid hormone, and glucose-sensitive beta- and alpha-cells of pancreatic islets secreting insulin and glucagon, respectively. We conclude this article with implications of this approach for pathophysiology and therapeutics, including defects in chief cell Ca(2+) sensitivity, resulting in the hyperparathyroidism of renal disease, and defects in biphasic insulin secretion, resulting in diabetes mellitus.
 ...
PMID:Unifying concepts in stimulus-secretion coupling in endocrine cells and some implications for therapeutics. 1974 43

Urinary albumin excretion is a powerful predictor of progressive cardiovascular and renal disease. In rats and humans, administration of a synthetic vasopressin analogue, 1-desamino-8-D-arginine-vasopressin, increases urinary albumin excretion; however, it is unknown if endogenous vasopressin levels influence albumin excretion. To determine this we measured copeptin, a marker of endogenous vasopressin levels, and its association with urinary albumin excretion in 7593 patients in the PREVEND study, a prospective population based, observational cohort. Urinary albumin excretion was measured in two consecutive 24-h urine samples by nephelometry while copeptin was measured by an immunoassay. Median copeptin concentrations were significantly higher in males than females and high levels were associated with significantly lower 24-h urine volumes of high osmolarity. With increasing quintiles of copeptin levels, the percentage of microalbuminuric subjects increased from 13 to 25 for males and from 8 to15 for females. This association was independent of age and other potential confounders; however, we found an interaction between age and copeptin in their association with urinary albumin excretion. Our study shows that plasma copeptin levels are associated with microalbuminuria, consistent with the hypothesis that vasopressin is involved in urinary albumin excretion. If future studies show that this association is causal, then drinking more water or pharmacological intervention to decrease plasma vasopressin may have beneficial effects on the kidney, especially in the elderly.
 ...
PMID:Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria in a large population cohort. 2001 Aug 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>