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)

Endothelin-1 (ET-1) is a pleiotropic hormone produced primarily by the endothelium. Synthesis of ET-1 is stimulated by the major signals of cardiovascular stress, such as vasoactive agents (angiotensin II, norepinephrine, vasopressin, and bradykinin), cytokines (e.g., tumor necrosis factor alpha and transforming growth factor beta), and other factors, including thrombin and mechanical stress. ET-1 induces vasoconstriction, is proinflammatory, promotes fibrosis, and has mitogenic potential, important factors in the regulation of vascular tone, arterial remodeling, and vascular injury. These effects are mediated via two receptor types, ETA and ETB. The role ET-1 plays in normal cardiovascular homeostasis and in mild essential hypertension in humans is unclear. However, certain groups of essential hypertensive patients may have ET-1-dependent hypertension, including blacks (subjects of African descent), salt-sensitive hypertensives, patients with low renin hypertension, and those with obesity and insulin resistance. ET-1 has also been implicated in severe hypertension, heart failure, atherosclerosis, and pulmonary hypertension. In all of these conditions, plasma immunoreactive ET levels are elevated and tissue ET-1 expression is increased. Accordingly, it is becoming increasingly apparent that ET-1 plays an important role in cardiovascular disease and in some forms of hypertension in humans. Data from clinical trials using combined ETA-ETB receptor blockers have already demonstrated significant blood-pressure-lowering effects. Thus, targeting the endothelin system may have important therapeutic potential in the treatment of hypertension, particularly by contributing to the prevention of target organ damage and the management of cardiovascular disease.
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PMID:Role of endothelin in human hypertension. 1283 65

Dopamine is an important regulator of blood pressure. Its actions on renal hemodynamics, epithelial transport and humoral agents such as aldosterone, catecholamines, endothelin, prolactin, pro-opiomelanocortin, renin and vasopressin place it in central homeostatic position for regulation of extracellular fluid volume and blood pressure. Dopamine also modulates fluid and sodium intake via actions in the central nervous system and gastrointestinal tract, and by regulation of cardiovascular centers that control the functions of the heart, arteries and veins. Abnormalities in dopamine production and receptor function accompany a high percentage of human essential hypertension and several forms of rodent genetic hypertension. Some dopamine receptor genes and their regulators are in loci linked to hypertension in humans and in rodents. Furthermore, single nucleotide polymorphisms (SNPs) of genes that regulate dopamine receptors, alone or via the interaction with SNPs of genes that regulate the renin-angiotensin system, are associated with human essential hypertension. Each of the five dopamine receptor subtypes (D1, D2, D3, D4 and D5) participates in the regulation of blood pressure by mechanisms specific for the subtype. Some receptors (D2 and D5) influence the central and/or peripheral nervous system; others influence epithelial transport and regulate the secretion and receptors of several humoral agents (e.g., the D1, D3 and D4 receptors interact with the renin-angiotensin system). Modifications of the usual actions of the receptor can produce blood pressure changes. In addition, abnormal functioning of these dopamine receptor subtypes impairs their antioxidant function.
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PMID:Regulation of blood pressure by dopamine receptors. 1461 Mar 23

Hypertension is a very common condition and the most important risk factor for the occurrence of cardiovascular events. The hyperactivity of the renin-angiotensin-aldosterone system is considered a cardiovascular risk factor in subjects with essential hypertension. The intrinsic vascular abnormality in which the renin-angiotensin-aldosterone system is clearly the milieu for the development of the pathologic changes in blood vessel walls is one of the causes of the establishment of hypertension. Many drugs with different mechanisms of action have been used for the treatment of hypertension and its vascular complications. Nevertheless, the utilities of many drugs are limited by their adverse effects. Continuous research in the search for new pharmacological agents for the treatment of hypertension has led to the development of angiotensin II receptor type AT1 blockers. The most important functions mediated by AT1 receptors include: vasoconstriction, induction of the production and release of aldosterone, renal reabsorption of sodium, cardiac cellular growth, proliferation of vascular smooth muscle, increase of peripheral noradrenergic action and the central activity of the sympathetic nervous system, stimulation of vasopressin release, and inhibition of renin release from the kidney. The angiotensin II receptor type AT1 blockers inhibit the interaction of angiotensin II with its AT1 receptor. These agents lower blood pressure without producing cough as a side effect since, unlike the angiotensin-converting enzyme inhibitors they do not influence the levels of bradykinin or substance P. Hence, these drugs are suitable for the treatment of hypertensive patients who require therapy with a drug blocking the effect of angiotensin-converting enzyme but cannot use angiotensin-converting enzyme inhibitors due to cough as a side effect.
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PMID:Role of angiotensin II AT1 receptor blockers in the treatment of arterial hypertension. 1462 77

The amiloride-sensitive epithelial sodium channel (ENaC), a multimeric plasma membrane protein composed of alpha-, beta-, and gamma-ENaC subunits, mediates Na(+) reabsorption in epithelial tissues, including the distal nephron, colon, lung, and secretory glands, and plays a critical role in pathophysiology of essential hypertension and cystic fibrosis (CF). The function of ENaC is tightly regulated by signals elicited by aldosterone, vasopressin, agents that increase intracellular cAMP levels, ions, ion channels, G-protein-coupled mechanisms, and cytoskeletal proteins. In this paper, the effects of Ca(2+) on the expression of the human ENaC subunits expressed in human embryonic kidney cells (HEK-293 cells) were examined. Incubation of cells with increased extracellular Ca(2+) and treatment of cells with A23187 and thapsigargin stimulated the expression of the monomeric ENaC subunits. Treatment of cells with Ca(2+)-chelating agents, EGTA and BAPTA-AM, reduced the levels of ENaC subunit expression. The pulse-chase experiments suggested that a rise in the intracellular Ca(2+) increases the ENaC subunit expression. Immunoblot analysis using the anti-ubiquitin antibody indicated that ENaC undergoes ubiquitination. A correlation between the processes that regulate ENaC function with the intracellular Ca(2+) was discussed.
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PMID:Role of intracellular Ca2+ in the expression of the amiloride-sensitive epithelial sodium channel. 1467 Mar 68

Renal sodium handling is an essential physiologic function in mammal for body fluid maintenance and blood pressure regulation. Recent advances in molecular biology have led to the identification of kidney-specific sodium transporters in the renal tubule, thereby supplying vast information for renal physiology as well as systemic physiology. Renal urinary concentration for body fluid maintenance is accomplished by counter current multiplication in the distal tubule. Sodium transport in the thick ascending limb of Henle (TAL) is the initial process of this system. We have demonstrated that renal urinary concentration is regulated in part by the expression of the Na(+)-K(+)-2Cl(-) co-transporter (BSC1) in TAL, by showing two mechanisms of BSC1 expression: pitressin vasopressin (AVP)-dependent and AVP-independent mechanisms. Two additional findings, namely, a lack of the ability to increase BSC1 expression leads to urinary concentrating defect and an enhanced BSC1 expression underlies the edema-forming condition, confirm the close association between sodium handling in TAL and body fluid accumulation. The lines of evidence from our genetic studies of the general Japanese population suggest the importance of mendelian hypertension genes in the genetic investigation of essential hypertension. Because those genes directly or indirectly regulate sodium transport by the Na-Cl co-transporter or the epithelial sodium channel in the distal convoluted tubule to the collecting duct (distal tubular segments after TAL), sodium handling in this part of the renal tubule may be, at least in part, involved in blood pressure regulation. The unveiling of such physiologic roles of sodium handling based on the sodium transporters or on the tubular segments may lead to a better understanding of systemic physiology as well as to the development of novel therapy for body fluid or blood pressure disorders.
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PMID:Renal sodium handling for body fluid maintenance and blood pressure regulation. 1517 65

Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. All of the five dopamine receptor genes (D1, D2, D3, D4, and D5) expressed in mammals and some of their regulators are in loci linked to hypertension in humans and in rodents. Under normal conditions, D1-like receptors (D1 and D5) inhibit sodium transport in the kidney and the intestine. However, in the Dahl salt-sensitive and spontaneously hypertensive rats, and humans with essential hypertension, the D1-like receptor-mediated inhibition of sodium transport is impaired because of an uncoupling of the D1-like receptor from its G protein/effector complex. The uncoupling is genetic, and receptor-, organ-, and nephron segment-specific. In human essential hypertension, the uncoupling of the D1 receptor from its G protein/effector complex is caused by an agonist-independent serine phosphorylation/desensitization by constitutively active variants of the G protein-coupled receptor kinase type 4. The D5 receptor is also important in blood pressure regulation. Disruption of the D5 or the D1 receptor gene in mice increases blood pressure. However, unlike the D1 receptor, the hypertension in D5 receptor null mice is caused by increased activity of the sympathetic nervous system, apparently due to activation of oxytocin, V1 vasopressin, and non-N-methyl D-aspartate receptors in the central nervous system. The cause of the activation of these receptors remains to be determined.
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PMID:D5 dopamine receptor knockout mice and hypertension. 1552 60

Vasopressin (AVP), an antidiuretic hormone, is known to induce hypervolemia and to regulate the renal expression of aquaporin-2 (AQP2) water channels, but it is not yet known whether the latter are involved in the pathogenesis of essential hypertension. The aim of the present study was therefore to make a comparative study of blood pressure (BP), urinary volume (UV), urinary osmolarity (uOsm), urinary AQP2 (uAQP2), and plasma AVP levels (PAVP) in male spontaneously hypertensive rats (SHR; n = 30) at 3, 7, and 12 weeks of age and in male Wistar-Kyoto rats (WKY, n = 30), also after the subcutaneous administration of OPC-31260 (OPC), a human AVP V(2) receptor antagonist. At 3 weeks, SHR had markedly higher uOsm and lower UV levels than WKY. At 7 weeks, SHR were hypertensive, showing increased uAQP2, PAVP, and uOsm levels and a decreased UV. At 12 weeks, no significant changes were observed in this condition. At 7 and 12 weeks of age, OPC-treated WKY rats showed significant reduction in BP and uOsm and increase in UV with respect to untreated animals. From 3 weeks of age, OPC-treated SHR presented significantly lower BP levels, higher UV levels, and lower uOsm than untreated animals. In treated WKY and SHR, uAQP2 levels were lower than in untreated animals. The PAVP appeared to be higher in OPC-treated rats from both strains. These findings suggest that AVP and the AQP2 are involved in the pathogenesis of hypertension in SHR.
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PMID:Aquaporin-2 water channels in spontaneously hypertensive rats. 1560 25

Bradykinin (BK) is one of the most important peptides regulating vascular tone, water, and ionic balance in the body, playing a key role in controlling BP. It is interesting that patients with essential hypertension excrete less BK than normotensive individuals. For elucidating the mechanism by which BK regulates renal water transport that contributes to its antihypertensive effect, aquaporin 2 (AQP2)-transfected collecting duct CD8 cells, expressing the BK type II receptor (BK2R), were used as an experimental model. In CD8 cells, BK pretreatment impaired forskolin-induced AQP2 translocation to the apical plasma membrane. For clarifying the signal transduction cascade associated with this effect, whether BK induced an increase in cytosolic calcium, via the G protein Gq, known to be coupled to BK2R, first was investigated. Spectrofluorometry using fura-2-AM revealed that 100 nM BK elicited a significant increase in Ca(i), which was abolished by the receptor antagonist HOE-140. BK acts through BK2R coupled to both Gq and Galpha13, a known upstream effector of Rho protein. In CD8 cells, BK causes an increase in Rho activity, likely as a result of Galpha13 activation. This results in stabilization of the cortical F-actin network, thus impairing AQP2 trafficking. These effects counteract physiologic vasopressin stimulation, which instead has an opposite effect on actin network organization through Rho inactivation.
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PMID:Bradykinin signaling counteracts cAMP-elicited aquaporin 2 translocation in renal cells. 1609 49

Improper functioning of kidneys plays a significant part in the development and further worsening of hypertension. The author aimed at studying the functional and hormonal activity of kidneys in patients with I-III stage essential hypertension under physiological hyperhydratation. 68 patients with essential hypertension and 21 patients of a control group have been observed. The blood content of hormones was detected before and after the physiological water stress consisting 2% of body weight. They are the following: rennin, angiotensin, aldosterone, vasopressin, and atrial sodium-releasing hormone. The observed patients with I stage essential hypertension mostly have their kidneys' ducts apparatus reconstructed with considerable decrease in water reabsorption in ducts apparatus of kidneys. It came along with high level of sodium excretion and moderate activation of rennin-angiotenstin-aldosterone system. Patients with II and III stage essential hypertension responds to the physiological water stress (in contrast to patients with I stage essential hypertension and patients of the control group) with progressive increase in water reabsorption in ducts apparatus of kidneys, decrease in sodium excretion comes along with high level of aldosterone, vasopressin and atrial sodium-releasing hormones.
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PMID:[Role of hormones in volume regulating kidney function in patients with hypertension]. 1615 6

This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counterregulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development of chronic liver disease, and arterial hypertension is rarely manifested in patients with cirrhosis, even in those with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This probably includes the combination of vasodilatation and vasoconstriction in parallel.
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PMID:Arterial hypertension and chronic liver disease. 1617 91


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