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)

Nocturnal polyuria is common in the elderly. In this condition the normal circadian rhythm of urine production is reversed so that urine flow is higher at night than during the day. Elderly men with nocturnal polyuria are commonly referred for prostate surgery, which, not surprisingly, fails to relieve their symptoms. Compared with controls, patients with nocturnal polyuria have higher nocturnal sodium excretion but not higher nocturnal free-water clearance. Similar results have been obtained in children with nocturnal enuresis. Use of vasopressin analogues to induce water retention in elderly patients with nocturnal polyuria is illogical and potentially hazardous; nocturia can be more safely alleviated by diuretic therapy. Nocturnal polyuria in the elderly is associated with hypertension: this is consistent with studies in younger age groups that show that essential hypertension is associated with nocturia and with increased night/day ratios for sodium excretion. We propose that nocturnal polyuria and essential hypertension share some of the same pathophysiological determinants. Specifically, we suggest that a defect in the nitric-oxide pathway may lead to resetting of the pressure-natriuresis relation in the kidney, sodium retention, and compensatory nocturnal natriuresis. This suggestion is consistent with evidence that ageing and essential hypertension are both associated with defects in the nitric-oxide pathway. Our hypothesis has obvious therapeutic implications. More generally, studying the pathogenesis of nocturnal polyuria in the elderly may advance our understanding of the pathogenesis of essential hypertension.
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PMID:Relation of nocturnal polyuria of the elderly to essential hypertension. 1084 Nov 44

The prevalence of essential hypertension in blacks is much higher than that in whites. In addition, the pathogenesis of hypertension appears to be different in black patients. For example, black patients present with a salt-sensitive hypertension characterized by low renin levels. Racial differences in renal physiology and socioeconomic factors have been suggested as possible causes of this difference, but reasons for this difference remain unclear. Endothelial cells are important in the regulation of vascular tonus and homeostasis, in part through the secretion of vasoactive substances. One of these factors, endothelin-1 (ET-1), is a 21 amino acid residue peptide with potent vasopressor actions. In addition to its contractile effects, it has been shown to stimulate mitogenesis in a number of cell types. Moreover, ET-1 displays modulatory effects on the endocrine system, including stimulation of angiotensin II and aldosterone production and inhibition of antidiuretic hormone in the kidney. Recent data from several laboratories indicate that ET-1 is overexpressed in the vasculature in several salt-sensitive models of experimental hypertension. Moreover, circulating plasma ET-1 levels are significantly increased in black hypertensives compared with white hypertensives. Thus, the ET system might be particularly important in the development or maintenance of hypertension in this population.
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PMID:Hypertension in black patients: an emerging role of the endothelin system in salt-sensitive hypertension. 1090 13

During the past decade, it has become evident that dopamine plays an important role in the regulation of fluid and electrolyte balance and blood pressure. Dopamine exerts its actions through two families of dopamine receptors, designated D1-like and D2-like, which are identical in the brain and in peripheral tissues. The two D1-like receptors--D1 and D5 receptors--expressed in mammals are linked to stimulation of adenylyl cyclase. The three D2-like receptors--D2, D3, and D4,--are linked to inhibition of adenylyl cyclase. Dopamine affects fluid and electrolyte balance by regulation of renal excretion of electrolytes and water through actions on renal hemodynamics and tubular epithelial transport and by modulation of the secretion and/or action of vasopressin, renin, aldosterone, catecholamines, and endothelin B receptors (ETB) receptors. It also affects fluid and sodium intake by way of "appetite" centers in the brain and alterations of gastrointestinal tract transport. The production of dopamine in neural and non-neural tissues and the presence of receptors in these tissues suggest that dopamine can act in an autocrine or paracrine fashion. This renal autocrine-paracrine function, which becomes most evident during extracellular fluid volume expansion, is lost in essential hypertension and in some animal models of genetic hypertension. This deficit may be caused by abnormalities in renal dopamine production and polymorphisms or abnormal post-translational modification and regulation of dopamine receptor subtypes.
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PMID:Renal dopamine and sodium homeostasis. 1098 Nov 46

Abnormalities in autonomic activity resulting in disturbances of the diurnal rhythm of many physiologic processes were recently revealed in hypertensive patients. These findings suggest deteriorations in the functioning of the suprachiasmatic nucleus (SCN), which is known to be the biological clock of mammals. To test this hypothesis, we carried out an immunocytochemical study of the SCN of primary hypertension patients who had died due to myocardial infarction or brain hemorrhage, and compared them with those of individuals with a normal blood pressure who had never had any autonomic disturbances and died from myocardial infarction after chest trauma or from hypothermia. We found that the staining for the three main neuronal populations of the SCN; i.e., vasopressin, vasoactive intestinal polypeptide, and neurotensin, reduced by more than 50% in the hypertensives compared with controls. The present data indicate a serious dysregulation of the biological clock in hypertensive patients. Such a disturbance may cause a harmful hemodynamic imbalance with a negative effect on circulation, especially in the morning, when the inactivity-activity balance changes. The difficulty in adjusting from inactivity to activity might be involved in the morning clustering of cardiovascular events.
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PMID:Neuropeptide changes in the suprachiasmatic nucleus in primary hypertension indicate functional impairment of the biological clock. 1117 8

Polymorphism of the dopamine receptor type-2 (D(2)) gene is associated with essential hypertension. To assess whether D(2) receptors participate in regulation of blood pressure (BP), we studied mice in which the D(2) receptor was disrupted. In anesthetized mice, systolic and diastolic BPs (in millimeters of mercury) were higher in D(2) homozygous and heterozygous mutant mice than in D(2)+/+ littermates. BP after alpha-adrenergic blockade decreased to a greater extent in D(2)-/- mice than in D(2)+/+ mice. Epinephrine excretion was greater in D(2)-/- mice than in D(2)+/+ mice, and acute adrenalectomy decreased BP to a similar level in D(2)-/- and D(2)+/+ mice. An endothelin B (ET[B]) receptor blocker for both ET(B1) and ET(B2) receptors decreased, whereas a selective ET(B1) blocker increased, BP in D(2)-/- mice but not D(2)+/+ mice. ET(B) receptor expression was greater in D(2)-/- mice than in D(2)+/+ mice. In contrast, blockade of ET(A) and V(1) vasopressin receptors had no effect on BP in either D(2)-/- or D(2)+/+ mice. The hypotensive effect of an AT(1) antagonist was also similar in D(2)-/- and D(2)+/+ mice. Basal Na(+),K(+)-ATPase activities in renal cortex and medulla were higher in D(2)+/+ mice than in D(2)-/- mice. Urine flow and sodium excretion were higher in D(2)-/- mice than in D(2)+/+ mice before and after acute saline loading. Thus, complete loss of the D(2) receptor results in hypertension that is not due to impairment of sodium excretion. Instead, enhanced vascular reactivity in the D(2) mutant mice may be caused by increased sympathetic and ET(B) receptor activities.
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PMID:Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice. 1156 95

There is increased awareness of the role of dopamine in cardiovascular function, renal function and systemic blood pressure regulation. Growing evidence indicates that each of the five dopamine receptor subtypes participates in the regulation of blood pressure by mechanisms distinct for that particular subtype. Some dopamine receptors regulate blood pressure by influencing the central and peripheral nervous system, while others influence renal function and release of renin, aldosterone and vasopressin. This review summarizes the physiology and pathophysiology of the peripheral dopaminergic system and our current understanding of the role of individual dopamine receptors in the pathophysiology of human essential hypertension.
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PMID:Dopamine receptors in hypertension. 1168 63

Endothelins are a family of peptides, which comprises endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3), each containing 21 amino-acids. ET-1 is a peptide secreted mostly by vascular endothelial cells, the predominant isoform expressed in vasculature and the most potent vasoconstrictor currently known. ET-1 also has inotropic, chemotactic and mitogenic properties. In addition, it influences salt and water homeostasis through its effects on the renin-angiotensin-aldosterone system (RAAS), vasopressin and atrial natriuretic peptide and stimulates the sympathetic nervous system. The overall action of endothelin is to increase blood pressure and vascular tone. Therefore, endothelin antagonists may play an important role in the treatment of cardiac, vascular and renal diseases associated with regional or systemic vasoconstriction and cell proliferation, such as essential hypertension, pulmonary hypertension, chronic heart failure and chronic renal failure. Long-term anti-endothelin therapy may improve symptoms and favourably alter the progression of heart failure. Endothelin appears to participate in induction and progression of sclerotic renal changes, leading to progression to end-stage renal disease. Anti-endothelin therapy might offer additional benefits in the prevention of progression of chronic renal failure in addition to the known benefits of RAAS inhibition. Clinical trials have demonstrated potentially important benefits of endothelin antagonists for patients with essential hypertension, pulmonary hypertension and heart failure. Further studies are necessary to determine the role of anti-endothelin therapy in the treatment of cardiovascular diseases and determine the different roles of selective receptor antagonism vs. mixed ET(A/B)-receptor antagonism in human diseases.
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PMID:Role of endothelin in cardiovascular disease. 1198 41

Although the aldosterone-responsive segments of the nephron together reabsorb <10% of the filtered Na+, certain single-gene defects that affect the epithelial Na+ channel (ENaC) in the luminal membrane of the collecting duct (CD) or its regulation by aldosterone cause severe hypertension, whereas others cause salt wasting and hypotension. These rare defects illustrate the key role of the distal nephron in maintaining normal extracellular volume and blood pressure. Genetic defects that increase the Cl- conductance of the junctional complexes may also lead to salt retention and hypertension. Less dramatic alterations in regulatory actions of other hormones such as vasopressin (VP), either alone or with other genetic variations, diet, or environmental factors, may also produce Na+ retention or loss. Although VP acts primarily to regulate water balance, it is also an antinatriuretic hormone. Elevated basal plasma VP levels, and/or augmented VP release with increased Na+ intake, have been linked to essential hypertension in humans and in animal models of congestive heart failure and cirrhosis. Norepinephrine, dopamine, and prostaglandin E2 can inhibit the antinatriuretic effects of VP, and changes in the actions of these autocrine and paracrine regulators may also be involved in abnormal regulation of Na+ reabsorption.
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PMID:Abnormal regulation of ENaC: syndromes of salt retention and salt wasting by the collecting duct. 1211 May 5

To investigate the relationship between 12 candidate genes responsible for water regulation, sodium metabolism and membrane ion transport and essential hypertension (EH) in the Chinese. Linkage analysis of EH was performed in 95 Chinese nuclear families including 477 subjects using a technique of fluorescence-based gene scanning with 12 microsatellite markers. Markers were selected on the chromosomal regions covering 12 candidate genes responsible for regulating water and sodium metabolism and membrane ion transport. These candidate genes included sodium hydrogen exchanger 3, sodium hydrogen exchanger 5, chloride bicarbonate exchanger 3, sodium calcium exchanger 1, mineralocorticoid receptor, plasma membrane calcium ATPase 2, ATPase,Na/K transporting alpha, a-adducin, SA gene, kidney epithelial sodium channel-gamma, vasopressin receptor 1A, and 11beta-hydroxysteroid dehydrogenase type 2 genes. Two-point non-parametric linkage analysis (NPL), maximum LOD score analysis and transmission/disequilibrium test (TDT) were performed using the GENEHUNTER software package. The NPL analysis and LOD score suggested a significant linkage at D12S398 (Z = 2.08, p<0.05 and LOD score = 1.26, p<0.01, respectively). TDT indicated a significant disequilibrium of transmission at the locus chi2 = 9.00, p < 0.005). No significant linkages were found at the other loci tested (p > 0.05 or LOD < -1). In conclusion, D12S398, a marker near the vasopressin receptor 1A gene (V1AR), showed a positive linkage with EH based on the results of three statistical methods (NPL, LOD score, and TDT). This region warrants further exploration.
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PMID:Linkage analysis of twelve candidate gene loci regulating water and sodium metabolism and membrane ion transport in essential hypertension. 1235 53

Dopamine is an important transmitter in the CNS and PNS, critically regulating numerous neuropsychiatric and physiological functions. These actions of dopamine are mediated by five distinct receptor subtypes. Of these receptors, probably the least understood in terms of physiological functions is the D5 receptor subtype. To better understand the role of the D5 dopamine receptor (DAR) in normal physiology and behavior, we have now used gene-targeting technology to create mice that lack this receptor subtype. We find that the D5 receptor-deficient mice are viable and fertile and appear to develop normally. No compensatory alterations in other dopamine receptor subtypes were observed. We find, however, that the mutant mice develop hypertension and exhibit significantly elevated blood pressure (BP) by 3 months of age. This hypertension appears to be caused by increased sympathetic tone, primarily attributable to a CNS defect. Our data further suggest that this defect involves an oxytocin-dependent sensitization of V1 vasopressin and non-NMDA glutamatergic receptor-mediated pathways, potentially within the medulla, leading to increased sympathetic outflow. These results indicate that D5 dopamine receptors modulate neuronal pathways regulating blood pressure responses and may provide new insights into mechanisms for some forms of essential hypertension in humans, a disease that afflicts up to 25% of the aged adult population in industrialized societies.
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PMID:Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive. 1248 73


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