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)

This study evaluates the relative importance of several mechanisms possibly involved in the natriuresis elicited by slow sodium loading, i.e. the renin-angiotensin-aldosterone system (RAAS), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), atrial natriuretic peptide (ANP), oxytocin and nitric oxide (NO). Eight seated subjects on standardised sodium intake (30 mmol NaCl day(-1)) received isotonic saline intravenously (NaLoading: 20 micromol Na(+) kg(-1) min(-1) or approximately 11 ml min(-1) for 240 min). NaLoading did not change MAP or GFR (by clearance of (51)Cr-EDTA). Significant natriuresis occurred within 1 h (from 9 +/- 3 to 13 +/- 2 micromol min(-1)). A 6-fold increase was found during the last hour of infusion as plasma renin activity, angiotensin II (ANGII) and aldosterone decreased markedly. Sodium excretion continued to increase after NaLoading. During NaLoading, plasma renin activity and ANGII were linearly related (R = 0.997) as were ANGII and aldosterone (R = 0.999). The slopes were 0.40 pM ANGII (mi.u. renin activity)(-1) and 22 pM aldosterone (pM ANGII)(-1). Plasma ANP and oxytocin remained unchanged, as did the urinary excretion rates of cGMP and NO metabolites (NO(x)). In conclusion, sodium excretion may increase 7-fold without changes in MAP, GFR, plasma ANP, plasma oxytocin, and cGMP- and NO(x) excretion, but concomitant with marked decreases in circulating RAAS components. The immediate renal response to sodium excess appears to be fading of ANGII-mediated tubular sodium reabsorption. Subsequently the decrease in aldosterone may become important.
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PMID:Mechanisms of acute natriuresis in normal humans on low sodium diet. 1252 45

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.
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PMID:Salt appetite and the renin-angiotensin system: effect of oxytocin deficiency. 1295 13

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

Various childhood mood disorders are being treated with serotonin selective reuptake inhibitors (SSRIs) such as fluoxetine (Prozac(R)), yet limited data are available on their effects on serotonergic systems prior to maturation. This study investigated the effects of chronic fluoxetine treatment on 5-HT2A serotonin receptor-mediated neuroendocrine responses in young male rats. Prepubescent male rats were treated with saline or fluoxetine (10 mg/kg/day, i.p.) for 14 days, a treatment regimen producing maximal changes in postsynaptic 5-HT2A function in adults. Eighteen hours post-treatment, the rats received saline or increasing doses (0.5, 2.0, or 5.0 mg/kg, i.p.) of the 5-HT2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl ((+/-)-DOI). Trunk blood was obtained to determine changes in oxytocin, ACTH, corticosterone, and renin responses. Fluoxetine produced a small ( approximately 6%) but significant reduction in body weight gain, but no changes were observed in basal hormone levels. In both saline- and fluoxetine-treated rats, (+/-)-DOI increased plasma oxytocin levels in a dose-dependent manner. However, the magnitude of the oxytocin responses to all doses of (+/-)-DOI were markedly attenuated ( approximately 50%) in the fluoxetine-treated rats, indicating a functional reduction in the E(max) of 5-HT(2A) receptor-mediated oxytocin responses. In contrast, fluoxetine did not alter the (+/-)-DOI-induced increases in plasma ACTH, corticosterone, or renin. These data provide the first demonstration of selective neuroadaptive responses in 55-HT2A serotonin receptor function due to prepubescent treatment with fluoxetine. These data may be clinically relevant with respect to the use of selective serotonin reuptake inhibitors in children and adolescents.
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PMID:Fluoxetine treatment of prepubescent rats produces a selective functional reduction in the 5-HT2A receptor-mediated stimulation of oxytocin. 1608 47

We studied c-Fos staining in adult male rats after 48 h of water deprivation and after 46 h of water deprivation with 2 h of access to water or physiological saline. Controls were allowed ad libitum access to water and physiological saline. For immunocytochemistry, anesthetized rats were perfused with a commercially available antibody for c-Fos. Dehydration significantly increased plasma vasopressin (AVP), osmolality, plasma renin activity (PRA), hematocrit, and sodium concentration and decreased urinary volume. Fos staining was significantly increased in the median preoptic nucleus, organum vasculosum of the lamina terminalis, supraoptic nucleus (SON), and magnocellular and parvocellular paraventricular nucleus (PVN), as well as the area postrema, nucleus of the solitary tract (NTS), and rostral ventrolateral medulla (RVL). Rehydration with water significantly decreased AVP levels and Fos staining in the SON, PVN, and RVL and significantly increased Fos expression in the perinuclear zone of the SON, NTS, and parabrachial nucleus. Rehydration with water was associated with decreased urinary sodium concentration and hypotonicity, and hematocrit and PRA were comparable to levels seen after dehydration. After rehydration with saline, plasma osmolality, hematocrit, and PRA were not different from control, but plasma AVP and urinary sodium concentration were increased. In the SON, Fos staining was significantly increased, with a great percentage of the Fos cells also stained for oxytocin compared with water deprivation. Changes in Fos staining were also observed in the NTS, RVL, parabrachial nucleus, and PVN. Rehydration with water or saline produces differential effects on plasma AVP, Fos staining, and sodium concentration.
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PMID:Differential effects of water and saline intake on water deprivation-induced c-Fos staining in the rat. 1630 62

This study determined the effect of destruction of rostral ventrolateral medulla (RVLM)-C1 cells on integrated sympathetic and hormonal responses to hypotension or glucoprivation. Injection of anti-dopamine beta-hydroxylase-saporin into the RVLM resulted in 29-99% depletion of RVLM-C1 neurons and approximately 60% reduction in the number of A5 neurons. As in our previous study in unanesthetized rats, resting mean arterial pressure (MAP) was reduced by approximately 10 mmHg in rats with >80% depletion of RVLM-C1 cells compared with control rats, although resting heart rate (HR) did not differ significantly. In the present study, resting plasma levels of norepinephrine (NE) did not differ significantly between control rats and rats with >80% depletion of RVLM-C1 cells, although there was a tendency for RVLM-C1 lesioned rats to have lower levels. Also consistent with our previous study, hydralazine (HDZ)-evoked hypotension resulted in smaller increases in HR and plasma levels of NE in rats with >80% depletion of RVLM-C1 cells compared with control rats. Furthermore, the elevated plasma levels of posterior pituitary hormones vasopressin and oxytocin evoked by HDZ were blunted in RVLM-C1 lesioned rats compared with control rats, even though MAP fell to lower levels in the lesioned rats. Plasma renin activity, plasma osmolality, and plasma protein concentrations did not differ between control rats and rats with >80% depletion of RVLM-C1 neurons. In response to systemic administration of 2-deoxyglucose, the circulating level of epinephrine and the resulting hyperglycemia were attenuated in rats with >80% depletion of RVLM-C1 cells compared with control rats. These results demonstrate that RVLM-C1 cells, in addition to playing a role in acute cardiovascular reflexes, play an important role in integrated sympathetic and hormonal responses to homeostatic challenges such as hypotension and glucoprivation.
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PMID:Attenuation of homeostatic responses to hypotension and glucoprivation after destruction of catecholaminergic rostral ventrolateral medulla neurons. 1662 90

The research on components of the renin-angiotensin system delivered a broad image of angiotensin II-binding sites. Especially, immunohistochemistry (IHC) provided an exact anatomical localization of the AT(1) receptor in the rat brain. Yet, controversial results between in vitro receptor autoradiography and IHC as well as between immunohistochemical studies using various antisera started a vehement discussion concerning specificity and cross-reactivity of these antisera. In particular the magnocellular subdivision of the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) provided controversial results on the localization of AT(1) receptors. Both areas are known for angiotensin II-induced release of vasopressin (VP) and oxytocin (OXT). To evaluate the significance of the appropriate method of antigen retrieval and its relevance for the detection of AT(1) receptors we performed IHC on AT(1) receptors in paraformaldehyde-fixed and paraffin-embedded brain tissue of Sprague-Dawley rats using either the detergent Triton X-100 or microwave oven heating. This study demonstrates that heat-induced hydrolysis enhances the quality and quantity of immunoreactivity (IR) in IHC on AT(1) receptors. In the organum vasculosum lamina terminalis and in the parvocellular subdivisions of the PVN we report a distribution of AT(1)-like-IR similar to that observed with other methods. However, in addition, we provide evidence that distinct AT(1)-like-IR is also localized in few magnocellular neurons of the PVN and in few parvocellular neurons of the dorsal SON but not in magnocellular neurons of the SON. Moreover, parallel IHC indicates that few magnocellular OXT- or VP-releasing neurons of the PVN as well as parvocellular OXT-releasing neurons of the SON do also contain AT(1) receptors.
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PMID:The use of heat-induced hydrolysis in immunohistochemistry on angiotensin II (AT1) receptors enhances the immunoreactivity in paraformaldehyde-fixed brain tissue of normotensive Sprague-Dawley rats. 1701 Mar 18

The aim of this experiment was to compare the role of renin-angiotensin and sympathetic nervous system in post-haemorrhagic mechanism of oxytocin release. Oxytocin content in venous dialysates was determined by radioimmunoassay. In control rats the release of oxytocin into dialysates did not change during whole experiment. The injection of captopril induced 2-fold higher oxytocin release, but caused no change in oxytocin release after bleeding. Superior cervical ganglionectomy (SCGx) 20 days before, caused 5-fold higher increase in oxytocin release than in control group. Injection of captopril in rats after SCGx, did not decrease the high level of oxytocin in dialysate. However, bleeding increased oxytocin release and 1 hour after bleeding the highest - 14-fold increase, took place. In the contrary to 14-fold increase in oxytocin release in animals with superior cervical ganglia (SCG), bleeding after SCGx caused only 2-fold higher oxytocin release. When SCGx, bleeding and injection of captopril were done simultaneously, oxytocin release remained on the control concentration level. We assumed that blockade of renin angiotensin system and sympathetic dennervation prevent the increase in oxytocin release after bleeding. On basis of our present experiments, it can be assumed that, in posthaemorrhagic oxytocin release into the blood, sympathetic innervation derived from SCGx, as well as, renin-angiotensin system are involved.
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PMID:Oxytocin release after bleeding in rat: the role of sympathetic and renin-angiotensin system. 1722 86

Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and by interacting with vasoactive hormones/humoral factors, such as aldosterone, angiotensin, catecholamines, endothelin, oxytocin, prolactin pro-opiomelancortin, reactive oxygen species, renin, and vasopressin. Dopamine receptors are classified into D(1)-like (D(1) and D(5)) and D(2)-like (D(2), D(3), and D(4)) subtypes based on their structure and pharmacology. In recent years, mice deficient in one or more of the five dopamine receptor subtypes have been generated, leading to a better understanding of the physiological role of each of the dopamine receptor subtypes. This review summarizes the results from studies of various dopamine receptor mutant mice on the role of individual dopamine receptor subtypes and their interactions with other G protein-coupled receptors in the regulation of blood pressure.
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PMID:Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice. 1808

There are several mysteries about the normal physiology of pregnancy (1). Renal sodium and water reabsorption occurs despite an increase in total blood volume. Moreover, the renin-angiotensin-aldosterone system (RAAS) is also stimulated in normal pregnancy, even though an increase in total blood volume normally suppresses the RAAS and increases sodium excretion in the nonpregnant state. Water retention also occurs and leads to hypoosmolality in normal pregnancy, even though total blood volume is expanded. On rare occasions, an extreme polyuria occurs in pregnancy that is unresponsive to arginine vasopressin (AVP). The receptors whereby AVP and oxytocin stimulate the principal cell of the collecting duct, vascular smooth muscle, glomerular mesangial and endometrial cells are in need of clarification. The present study proposes potential mechanisms relating to systemic arterial vasodilation to explain some of the apparent dilemmas of pregnancy.
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PMID:Dilemmas in human and rat pregnancy: proposed mechanisms relating to arterial vasodilation. 2008 11


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