UNIPROT:P01185 - FACTA Search

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)

This study was undertaken to determine the effects of oxyhemoglobin on vasopressin-induced responses in cerebral arterioles. Rat intracerebral arterioles about 60 microns in diameter were isolated and cannulated using pipettes. Changes in diameter secondary to the extraluminal application of drugs were monitored through a video micro-scaler. Vasopressin produced a triphasic, dose-dependent response consisting of vasodilation (10(-11) M), vasoconstriction (10(-9)-10(-8) M) and a decrease in vasoconstriction (10(-7)-10(-6) M). Pretreatment with oxyhemoglobin (10(-5) M) abolished the vasodilation induced by the lower dose vasopressin and doubled the vasoconstriction induced by the higher dose. The combination of L-arginine (10(-4) M) and superoxide dismutase (600 U) restored low-dose vasopressin vasodilation and suppressed high-dose vasoconstriction in oxyhemoglobin-pretreated arterioles, while they showed little effect when used singly. This study indicates that oxyhemoglobin enhances vasopressin-induced constriction of intracerebral arterioles and these effects can be inhibited by the combination of L-arginine and superoxide dismutase.
...
PMID:Oxyhemoglobin enhancement of vasopressin-induced constriction in rat cerebral arterioles. 783 27

It is known that in vivo administration of desmopressin (DDAVP; a selective V2-vasopressin receptor agonist) results in prostacyclin-independent vasodilation. The in vitro effects of DDAVP and its mechanisms were examined using rat aortic strips. DDAVP from a concentration of 1 x 10(-9) M caused a concentration-dependent relaxation of the aorta precontracted with norepinephrine (10(-7) M) with intact endothelium. However, no relaxation was induced in aorta with the endothelium removed. The DDAVP-induced relaxation was not influenced by the presence of indomethacin but was inhibited by L-NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide (NO) synthesis. The inhibition by L-NMMA was reversed by the addition of L-arginine but not D-arginine. Further, the endothelium-dependent relaxation due to DDAVP was potentiated by superoxide dismutase, a scavenger of superoxide anions, and was inhibited by hemoglobin. DDAVP induced an increase in guanosine 3',5'-cyclic monophosphate levels in the aorta with endothelium but not in aorta without endothelium, and this was suppressed by L-NMMA and hemoglobin. The suppression by L-NMMA was also partially reversed by L-arginine but not by D-arginine. Two selective V2-receptor antagonists had no effect on the DDAVP-induced vasorelaxation. Selective V1-receptor antagonists (a peptidic and a nonpeptidic) caused a concentration-dependent but nonparallel shift to the right of the concentration-response curves to DDAVP. However, DDAVP did not affect the tension of the strip with or without endothelium in nonprecontracted aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Endothelium-dependent vasorelaxation evoked by desmopressin and involvement of nitric oxide in rat aorta. 838 36

The present study was designed to investigate the effect of fluid percussion brain injury (FPI) on vasopressin-induced pial artery vasodilation and the role of superoxide anion generation in those observed effects. In the piglet, it was observed previously the FPI produces pial artery constriction associated with free radical generation. Anesthetized piglets equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. FPI of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Vasopressin in physiological and pharmacological concentrations (10 and 1,000 microU/ml) produced vasodilation that was reversed to constriction after FPI (15 +/- 1 vs. -8 +/- 1 and 25 +/- 1 vs. 13 +/- 1% for 10 and 1,000 microU/ml before and after injury, respectively). Vasopressin-induced dilation was associated with increased cerebrospinal fluid guanosine 3', 5'-cyclic monophosphate, and these biochemical changes were blunted by FPI (407 +/- 12 and 720 +/- 28 vs. 4 and 272 +/- 5 fmol/ml for control and 10 microU/ml before and after injury, respectively). In contrast, polyethylene glycol superoxide dismutase (PEG-SOD) and catalase pretreatment 30 min before FPI partially restored vasopressin-induced pial artery dilation (14 +/- 1 vs. 3 +/- 1 and 22 +/- 1 vs. 2 +/- 4% for 10 and 1,000 microU/ml before and after FPI, respectively). Similarly, biochemical changes associated with vasopressin dilation were also partially restored by PEG-SOD and catalase after FPI. These data show that vasopressin is reversed from a dilator to a vasoconstrictor after FPI and suggests the superoxide anion generation contributes to the alteration of vasopressin cerebrovascular effects after injury and that such altered vasopressin cerebrovascular effects contribute to pial vasoconstriction after FPI.
...
PMID:Influence of brain injury on vasopressin-induced pial artery vasodilation: role of superoxide anion. 896 66

The role of superoxide in sepsis-altered hepatocyte Ca2+i regulation was studied by examining the effect of treatment of septic rats with superoxide dismutase-polyethylene glycol (SOD-PEG) on hepatocyte Ca2+ influx and efflux, and cytosolic [Ca2+]. Rats were implanted with sterile or bacteria-laden (Escherichia coli and Bacteroides fragilis) fecal pellets into the abdominal cavity. Eight hours after the implantation, rats were treated with SOD-PEG or its vehicle PEG. Septic and sterile implanted rats were killed 24 h postimplantation, and their livers were removed to isolate viable hepatocytes. Isolated hepatocytes were incubated with traces of 45Ca to assess Ca2+ influx and efflux. The 45Ca exchange assessments also allowed calculation of the intracellular exchangeable Ca2+ contents. [Ca2+]i was quantified by the use of fluorescent dye indo-1 and microfluorometric techniques. There were no differences in the Ca2+ influx, Ca2+ efflux, intracellular exchangeable Ca2+, or [Ca2+]i between the treated or untreated sterile and unoperated controls. However, compared with the nonseptic groups, the septic rats with or without administration of the vehicle (PEG) showed marked increases in Ca2+ influx, intracellular exchangeable Ca2+ and [Ca2+]i but not Ca2+ efflux. When challenged with vasopressin, the hepatocytes from septic rats, administered with PEG alone, did not elevate their [Ca2+]i as was characteristic of the hepatocytes from the nonseptic rats. The treatment of septic rats with SOD-PEG was effective in restoring Ca2+ influx, cellular exchangeable Ca2+, [Ca2+]i, and the [Ca2+]i response to vasopressin to levels found in the control and sterile groups. These findings support the concept that the generation of the superoxide free radical leads to Ca2+i-related derangements and related cell/organ dysfunction in sepsis.
...
PMID:Superoxide radical scavenging prevents cellular calcium dysregulation during intraabdominal sepsis. 911 Apr 11

To investigate the role of nitric oxide (NO) and its interaction with oxygen radicals in fever, we injected conscious rabbits intravenously (i.v.) with 1 microgram/kg bacterial lipopolysaccharide (LPS) and measured body temperatures, and circulatory and respiratory parameters. We estimated plasma levels of antidiuretic hormone (ADH); nitrate as a measure of NO metabolism under aerobic conditions; prostaglandin E2 (PGE2) and prostaglandin PGF2 alpha (PGF2 alpha); and tumor necrosis factor alpha (TNF alpha). We studied the effects of LPS before and after treatment with oxygen radical scavengers superoxide dismutase and catalase (SOD/CAT), before and after treatment with NG-monomethyl-L-arginine (L-NMMA), a specific blocker of nitric oxide synthase (NOS), before and after treatment with methylene blue (MB). N-methyl-D-aspartate (NMDA) receptors were blocked with ketamine. LPS increased core temperature by 1.1 +/- 0.1 degree C within 3 h, associated with a rapid increase of plasma TNF alpha, PGE2 and PGF2 alpha, and a fall of nitrate. The decrease of nitrate following LPS was augmented in rabbits pretreated with SOD/CAT, associated with a rise of core temperature of 1.6 +/- 0.1 degree C within 3 h. The lowest levels of nitrate were observed in rabbits pretreated with L-NMMA, associated with a rise of core temperature of 3.0 +/- 0.1 degree C within 3 h. Treating the same rabbits with a continuous i.v. infusion of 5 mg/kg/h MB, starting 30 min before injection of LPS, caused an immediate increase in nitrate and completely prevented fever. The rise of TNF alpha and ADH after LPS, however, was not significantly different from the control fever, and plasma PGE2 levels were nearly twice as elevated. MB also prevented fever in NMMA-treated rabbits, but only as long as nitrate levels remained elevated. MB induced an immediate rise of core temperature in ketamine-treated rabbits. We conclude that an undisturbed or elevated synthesis of NO in the central nervous system prevents fever, possibly via positive feedback action of NO on presynaptic glutaminergic neurons.
...
PMID:Antipyretic role of nitric oxide during endotoxin-induced fever in rabbits. 950 19

Angiotensin II (Ang II) has profound effects in the central nervous system (CNS), including promotion of thirst, regulation of vasopressin secretion, and modulation of sympathetic outflow. Despite its importance in cardiovascular and volume homeostasis, angiotensinergic mechanisms are incompletely understood in the CNS. Recently, a novel signaling mechanism for Ang II involving reactive oxygen species (ROS) has been identified in a variety of peripheral tissues, but the involvement of ROS as second messengers in Ang II-mediated signaling in the CNS has not been reported. The hypothesis that superoxide is a key mediator of the actions of Ang II in the CNS was tested in mice using adenoviral vector-mediated expression of superoxide dismutase (AdSOD). Changes in blood pressure, heart rate, and drinking elicited by injection of Ang II in the CNS were abolished by prior treatment with AdSOD in the brain, whereas the cardiovascular responses to carbachol, another central vasopressor agent, were unaffected. In addition, Ang II stimulated superoxide generation in primary CNS cell cultures, and this was prevented by the Ang II receptor (Ang II type 1 subtype) antagonist losartan or AdSOD. These results identify a novel signaling mechanism mediating the actions of Ang II in the CNS. Dysregulation of this signaling cascade may be important in hypertension and heart failure triggered by Ang II acting in the CNS.
...
PMID:Superoxide mediates the actions of angiotensin II in the central nervous system. 1245 82

To study the role of K(+) channels in the coronary and renal vascular response to vasopressin during diabetes mellitus, and whether there are gender differences in this role, we have examined the isometric response to this peptide of 2-mm-long arterial segments from male and female, normoglycemic and streptozotocin-induced diabetic rats. Vasopressin (10(-12)-3 x 10(-8) M) produced arterial concentration-dependent contraction, and during normoglycemia, this contraction was lower in coronary arteries from female than from male rats, and it was similar in renal arteries from both genders. This contraction was reduced by diabetes in coronary arteries, and increased in renal arteries, from both genders. The blocker of Ca(2+)-sensitive K(+) channels charybdotoxin (10(-7) M) increased the contraction to vasopressin in coronary arteries of diabetic females, but not in the other cases (diabetic males and normoglycemic females or males). This blocker also increased the contraction to vasopressin in renal arteries from diabetic, but not in those from normoglycemic female rats, and also increased it in a higher magnitude in arteries from diabetic than in those from normoglycemic male rats. The blocker of ATP-sensitive K(+) channels glybenclamide (10(-5) M) or the scavenger of superoxide radicals superoxide dismutase (100 U/ml) did not modify the contraction to vasopressin in any experimental group. These results suggest that diabetes activates the modulatory role of K(+) channels in the coronary and renal vasoconstriction to vasopressin, but it alters in a different way the vasoconstriction to vasopressin in these two types of arteries. The effects of diabetes on this vasoconstriction are not related to increased release of superoxide radicals.
...
PMID:Role of K(+) channels in the coronary and renal vascular reactivity to vasopressin in diabetic rats. 1280 50

Based on our previous results, we investigated whether cyclosporin A (CsA)-induced vasopressin type 1A receptor up-regulation was mediated by free radicals. We report that CsA analogues with different affinities for cyclophilin and calcineurin were able to up-regulate vasopressin type 1A receptor and to generate free radicals in smooth muscle cells independently of calcineurin. Further, we demonstrate that the antioxidant N-acetyl-L-cysteine blocked the increase in vasopressin type 1A receptor mRNA and protein levels induced by CsA and that low concentrations of prooxidants were able to directly increase vasopressin type 1A receptor mRNA and protein levels. In addition, short exposure to CsA or pro-oxidants was sufficient to significantly increase vasopressin type 1A receptor mRNA and protein levels. Using cell-permeable forms of superoxide dismutase and catalase, we finally show that superoxide mediates the CsA-induced effects on vasopressin type 1A receptor. These results provide strong evidence that CsA-induced superoxide generation is causally involved in vasopressin type 1A receptor expression and demonstrate for the first time that low physiological concentrations of radicals, most probably superoxide, are able to directly affect cellular signaling to increase vasopressin type 1A receptor expression in rat aortic smooth muscle cells.
...
PMID:Vasopressin type 1A receptor up-regulation by cyclosporin A in vascular smooth muscle cells is mediated by superoxide. 1292 65

The inner medullary collecting duct (IMCD) contains relatively high nitric oxide (NO) synthetic capacity, but the effect of NO on IMCD transport remains unclear. We determined the effect of NO on basal and vasopressin (AVP)-stimulated urea (Purea) and water (Pf) permeabilities in isolated, perfused rat IMCD. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) increased cGMP production in IMCD, but neither SNAP (10(-4) M) nor 8-BrcGMP (10(-4) M), the cell-permeable analog of cGMP, affected basal or AVP-stimulated Purea. The free radical superoxide is produced by oxidases in the kidney and can interact with NO. To determine the effect of superoxide generation on transport, IMCDs were incubated with diethyldithiocarbamate (DETC; 10(-3) M), the inhibitor of superoxide dismutase (SOD). DETC significantly increased basal and AVP-stimulated Purea (control: 28.7 +/- 4.5 vs. DETC: 40.9 +/- 6.2 x 10(-5) cm/s; P < 0.001; n = 9). Preincubation of IMCD with SNAP or the SOD mimetic tempol completely inhibited DETC-stimulated Purea. DETC caused a significant increase in superoxide generation by IMCD, and this was blocked by SNAP. Incubation of IMCD with the NO synthase (NOS) substrate l-arginine blocked the stimulatory effect of DETC on Purea, and this was reversed by the neuronal NOS inhibitor 7-nitroindazole. In contrast, neither basal nor AVP-stimulated Pf was affected by NO donors or DETC. In summary, exogenous or endogenously produced NO does not affect basal urea transport in the IMCD but inhibits superoxide-stimulated Purea. In the inner medulla, superoxide generation by local oxidases may stimulate urea transport, and the role of endogenous NO may be to dampen this effect by decreasing superoxide levels.
...
PMID:Nitric oxide inhibits superoxide-stimulated urea permeability in the rat inner medullary collecting duct. 1296 88

Hypertension, a powerful risk factor for stroke and dementia, has damaging effects on the brain and its vessels. In particular, hypertension alters vital cerebrovascular control mechanisms linking neural activity to cerebral perfusion. In experimental models of slow-developing hypertension, free radical signaling in the subfornical organ (SFO), one of the forebrain circumventricular organs, is critical for the hormonal release and sympathetic activation driving the elevation in arterial pressure. However, the contribution of this central mechanism to the cerebrovascular alterations induced by hypertension remains uncertain. We tested the hypothesis that free radical production in the SFO is involved in the alterations in cerebrovascular regulation produced by hypertension. In a mouse model of gradual hypertension induced by chronic administration of subpressor doses of angiotensin II (AngII), suppression of free radicals in the SFO by overexpression of CuZn-superoxide dismutase (CuZnSOD) prevented the alteration in neurovascular coupling and endothelium-dependent responses in somatosensory cortex induced by hypertension. The SFO mediates the dysfunction via two signaling pathways. One involves SFO-dependent activation of the paraventricular hypothalamic nucleus, elevations in plasma vasopressin, upregulation of endothelin-1 in cerebral resistance arterioles and activation of endothelin type A receptors. The other pathway depends on activation of cerebrovascular AngII type 1 (AT1) receptors by AngII. Both pathways mediate vasomotor dysfunction by inducing vascular oxidative stress. The findings implicate for the first time the SFO and its efferent hypothalamic pathways in the cerebrovascular alterations induced by AngII, and identify vasopressin and endothelin-1 as potential therapeutic targets to counteract the devastating effects of hypertension on the brain.
...
PMID:Central cardiovascular circuits contribute to the neurovascular dysfunction in angiotensin II hypertension. 2249 44

1 2 Next >>