Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To explore the role of oxytocin in the regulation of salt appetite and blood pressure, we conducted studies in oxytocin gene-knockout mice and determined (1) blood pressure and heart rate during day and night periods, (2) salt appetite after iso-osmotic volume depletion, and (3) salt appetite and blood pressure after central injection of angiotensin II. Long-term arterial catheters were inserted, and blood pressure and heart rate were recorded for 24 hours. There was a modest decrease in blood pressure and heart rate in knockout mice. Salt appetite was measured with a 2- bottle choice (water and 2% NaCl), with measurement of licking activity. Mice were injected subcutaneously with 30% polyethylene glycol (0.5 mL), and voluntary intakes were measured for 24 hours. Knockout mice consumed 3 times the amount of NaCl than did controls, 276+/-77 vs 90+/-38 licks/24 h (P<0.05). Water consumption was similar between groups. Angiotensin II (5, 50, and 200 ng/3 microL) injected intracerebroventricularly produced dose-related increases in intake, with no differences between the groups. The 50-ng dose of angiotensin II elicited salt and water intakes of 151+/-43 vs 160+/-33 licks and 250+/-53 vs and 200+/-51 licks, respectively (control vs knockout). The pressor response to angiotensin II was not different between the groups. Results suggest that oxytocin plays a role in the regulation of blood pressure and salt appetite, specifically as mediated by volume receptors, and that the renin-angiotensin system is not involved in these changes.
Hypertension 2003 Oct
PMID:Salt appetite and the renin-angiotensin system: effect of oxytocin deficiency. 1295 13

Current guidelines for dialysis in pregnant women have been developed in response to occasional dialysis patients who unexpectedly become pregnant. These include prolonged dialysis times, generally 20 or more hours per week. The increased dialysis time requires careful monitoring of phosphorus and potassium which may be removed in excessive amounts. Target serum bicarbonate for a pregnant woman is 18-20 mEq/L. Patients require increased supplementation of water soluble vitamins particularly folate. Increased doses of erythropoietin are needed to meet the demands for increased red cell production occasioned by pregnancy. Hypertension is the greatest danger to the mother and extreme vigilance is required up to six weeks postpartum. Volume status is difficult to predict and can only be determined by repeated clinical assessment. Only 50% of pregnancies result in a surviving infant and in the best subgroups, no more than 75% of pregnancies are successful. Over 80% of live born infants are premature, often severely premature. The key to improving the outcome of pregnancy in dialysis patients lies in decreasing premature labor and premature rupture of membranes in the late second and early third trimester. To this end, it is important for obstetricians to recognize that the risk of prematurity in pregnant dialysis patients is as higher or higher than in any other group and that any intervention, including such measures as progesterone and oxytocin antagonists, used to prevent premature labor in other groups should be considered in dialysis patients.
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PMID:Pregnancy in dialysis patients: where do we go from here? 1296 89

Transient receptor potential channel proteins (TRPs) constitute a steadily growing family of ion channels with a range of purported functions. It has been demonstrated that TRPV2 is activated by moderate thermal stimuli and, in the rat, is expressed in medium to large diameter dorsal root ganglion neurons. In this study, antisera specific for the human TRPV2 homologue were raised and characterized for immunohistochemical use. Subsequently, thorough investigation was made of the localization of this cation channel in the macaque primate brain. TRPV2-immunoreactive material was highly restrictively localized to hypothalamic paraventricular, suprachiasmatic, and supraoptic nuclei. Confocal double- and triple-labeling studies demonstrated that TRPV2 immunoreactivity is preferentially localized to oxytocinergic and vasopressinergic neurons. Few, if any, cells in these regions expressed TRPV2 immunoreactivity in the absence of oxytocin immunoreactivity or vasopressin immunoreactivity. Expression in the paraventricular and supraoptic nuclei suggests that TRPV2 is likely to play a fundamental role in mediating cation transport in neurohypophysial neurons. TRPV2 has been shown to be translocated upon cell activation and neurons expressing TRPV2 immunoreactivity in vivo are among those known to engage in sporadic, intense activity. Taken together, these data suggest that this channel may play a vital role in mediating physiological activities associated with oxytocin and vasopressin release such as parturition, lactation, and diuresis. These data may also implicate the involvement of TRPV2 in disorders of the hypothalamic-pituitary-adrenal axis, including anxiety, depression, hypertension, and preterm labor.
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PMID:Discrete expression of TRPV2 within the hypothalamo-neurohypophysial system: Implications for regulatory activity within the hypothalamic-pituitary-adrenal axis. 1515 77

In this paper, we review our current understanding of the medicinal chemistry of the major peptide systems, which influence body fluid homeostasis. Electrolytes play pivotal roles in intra- and intercellular communication, acid-base equilibrium and, when bound to several macromolecules, they regulate a myriad of enzymatic proteins, receptors and transcription factors. Cell turgor influences the plasma membrane, which activates mechanically-gated ion channels or mechanoreceptors, and the expression of a number of genes which underlie long-term metabolic responses to hormones, substrates and reactive oxygen intermediates. The altered kinetics and enzymatic cleavage of peptides during water-electrolyte imbalance can contribute to cardiac and renal damage associated with elevated blood pressure. Identification of the enzymes which are responsible for cleavage, together with emerging information about the mechanisms of action and structures of regulatory and effector peptides, has laid a foundation for the discovery of novel drugs, some of which are in use or are now undergoing evaluation in experimental trials. The development of models of hydrosaline challenge with relative efficiency to induce selective water-electrolyte imbalance has permitted the identification of kallikrein-kinin, renin-angiotensin-aldosterone, vasopressin-oxytocin, thyrotropin-releasing hormone and luteinizing hormone-releasing hormone as susceptible substrates. At present, the angiotensin-I converting enzyme inhibitors are well-known efficacious, orally active, blood pressure-lowering agents which have been used in hypertensive patients. In addition to several new analogues of this class of drug, some selective dual inhibitors of angiotensin-I converting enzyme and neutral endopeptidase and inhibitors of aminopeptidases are now also being rationally assayed and their beneficial effects on hypertension and hydromineral balance indicate that this type of drug may have powerful therapeutic effects for disorders of body fluid homeostasis.
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PMID:Peptide metabolism and the control of body fluid homeostasis. 1532 Jul 88

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) and oxytocin (OT) are cyclic nonapeptides whose actions are mediated by the stimulation of specific G-protein-coupled receptors (GPCRs) currently classified into V(1)-vascular (V(1)R), V(2)-renal (V(2)R) and V(3)-pituitary (V(3)R) AVP receptors and OT receptors (OTR). The signal transduction pathways coupled to the different subtypes of AVP/OT receptors are reviewed. The recent cloning of the different members of the AVP/OT family of receptors now allows the extensive characterisation of the molecular determinants involved in agonist and antagonist binding, as well as signal transduction coupling. Potential therapeutic uses of AVP receptor antagonists include: the blockade of V(1)-vascular AVP receptors in arterial hypertension, congestive heart failure (CHF) and peripheral vascular diseases; the blockade of V(2)-renal AVP receptors in the syndrome of inappropriate vasopressin secretion, CHF, liver cirrhosis, nephrotic syndrome and any state of excessive retention of free water and subsequent hyponatraemia; the blockade of V(3)-pituitary AVP receptors in adrenocorticotropin (ACTH)-secreting tumours. The pharmacological and clinical profile of orally-active non-peptide AVP receptor antagonists is reviewed.
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PMID:Development and therapeutic indications of orally-active non-peptide vasopressin receptor antagonists. 1599 64

To identify defects in the salt-sensitive Dahl rat (Dahl-S), the natriuretic, catecholaminergic and pressor responses to 60-min elevation of the cerebroventricular sodium concentration (CNS-induced natriuresis) were compared between prehypertensive salt-sensitive Dahl-S and salt-resistant Dahl rats (Dahl-R). The plasma concentrations of the rat natriuretic hormone oxytocin, which has implications for the development of hypertension, and vasopressin (AVP) were also measured. Basal sodium and catecholamine excretion and mean arterial blood pressure (MAP) were similar in both strains. Sodium excretion during CNS stimulation increased more than 15-fold in Dahl-R but only 10-fold in Dahl-S. Dopamine excretion increased only transiently and similarly in both strains. Noradrenaline excretion and response to CNS stimulation were similar, suggesting a comparable sympathetic nervous activity between the strains. MAP increased comparably in Dahl-R and Dahl-S. Plasma AVP concentration was similar in both strains while plasma oxytocin concentration after CNS stimulation was more than 2-fold higher in Dahl-S than in Dahl-R. In conclusion, the prehypertensive Dahl-S has an attenuated natriuretic response to elevations of the cerebroventricular fluid sodium concentration and a higher plasma level of the natriuretic hormone oxytocin. Dopamine is not a mediator of CNS-induced natriuresis in neither strain. The attenuated natriuretic response may partly explain the salt-sensitivity in Dahl-S, and the higher plasma oxytocin value may either represent an effort to compensate for the deficient natriuretic response or reflect a primary defect in this system. Due to the known involvement of oxytocin in central MAP regulation in some hypertensive animal models, the findings warrant further investigation.
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PMID:CNS-induced natriuresis, neurohypophyseal peptides and renal dopamine and noradrenaline excretion in prehypertensive salt-sensitive Dahl rats. 1609 5

We have previously shown that exercise training activates nucleus tractus solitarii (NTS) oxytocinergic projections, resulting in blunted exercise tachycardia. The objective of this study was to determine the effects of hypertension and training on oxytocin (OT) and OT receptor expression in the hypothalamic paraventricular nucleus (PVN) and projection areas (dorsal brain stem [DBS]). Male, normotensive, Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were trained (55% maximal exercise capacity, 3 months) or kept sedentary, and pressure was measured weekly. DBS sections were processed for immunohistochemistry (polyclonal guinea pig anti-OT) or in situ hybridization for OT and OT receptor (35S-oligonucleotide probes). Other groups of rats had brains removed and frozen to isolate the DBS and PVN; samples were processed for OT and OT receptor cDNA reverse transcription-polymerase chain reaction amplification with beta-actin as the housekeeping gene. Training was equally effective in improving running distance in both groups, with pressure reduction only in SHR (-10%, P<0.05). In trained WKY, baseline bradycardia (P<0.05) occurred simultaneously with increased NTS OT immunostaining and mRNA expression (+3.5-fold), without any change in OT receptor mRNA expression. PVN OT mRNA and DBS OT receptor mRNA expressions were significantly lower in SHR versus WKY (-39% and -56%, respectively). Training did not alter DBS OT receptor density in the SHR group but increased OT mRNA in both PVN and DBS areas (+78% and +45%, respectively). Our results show a marked hypertension-induced reduction in OT receptor mRNA expression, not altered by training. In contrast, training increased OT mRNA expression in sedentary and hypertensive rats, which may facilitate training-induced cardiac performance.
Hypertension 2005 Oct
PMID:Hypertension and exercise training differentially affect oxytocin and oxytocin receptor expression in the brain. 1615 94

Hyponatremia can be classified as acute or chronic depending on its duration, and treatment options are tailored to this classification. However, it is sometimes difficult to differentiate acute from chronic hyponatremia in the Emergency Department (ED). The objective of this study was to identify characteristics to help diagnose and manage acute hyponatremia in the ED. Patients with acute hyponatremia in the ED were enrolled from a retrospective 2-year chart review. Eleven patients (0.8%) were identified with acute hyponatremia out of a total of 1321 hyponatremic patients. There were nine women and two men. The mean age was 48.9 years. The mean sodium (Na(+)) level was 115+/-4 mmol/L. Accompanying biochemical abnormalities included hypouricemia and hypouremia with increased fractional excretions of uric acid (UA) and urea. The estimated amount of water intake ranged from 2.5 to 10 liters (mean, 5.1+/-2.3 liters) during the day before ED presentation. All patients were treated with hypertonic saline and furosemide at a correction rate of 1.6+/-0.5 mmol/L/h. No patients had neurological sequelae after treatment. The causes of acute hyponatremia included induction of abortion with oxytocin (n=1), primary polydipsia on neuroleptic agents (n=2), polyethylene glycol (PEG) preparation for colonoscopy (n=1), diuretic therapy for hypertension (n=4), ecstasy use (n=1), and weight-reducing herbal teas (n=2). We conclude that in the right clinical setting, high free water intake and low serum urea and UA favor acute hyponatremia. A detailed drug history may be helpful in the differential diagnosis of acute hyponatremia.
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PMID:Biochemical and etiological characteristics of acute hyponatremia in the emergency department. 1624 91

Brazil has one of the world's highest cesarean section rates. Contributing factors include the organization of obstetric practice, physicians' attitudes, and women's preferences and decisions. This study aimed to identify factors associated with cesarean sections in a public maternity hospital in Rio de Janeiro. A case-control study was conducted with 231 cesarean sections (cases) and 230 vaginal deliveries (controls). Hierarchical logistic regression analysis was performed, based on a conceptual model. Factors associated with increased odds of cesarean section were: primiparity; mother's age 20-34; last birth by cesarean; cervical dilatation < 3cm at admission; patient request; daytime birth; male attending obstetrician; obstetrician on duty for more than 24 hours a week; obstetrician with private practice; gestational hypertension; non-cephalic presentation; and gestational age > 41 weeks. Factors associated with lower odds of cesarean were: gestational age < 37 weeks; leaving home with signs of labor, use of oxytocin; and amniotomy. In this hospital, interventions aimed to modify the above-mentioned factors can help lower the cesarean rate.
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PMID:Factors associated with cesarean sections in a public hospital in Rio de Janeiro, Brazil. 1695 78


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