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)

Renal cortical prostaglandin synthesis, particularly by arterioles and glomeruli, is important to preserve renal blood flow (RBF) and glomerular filtration rate (GFR). Glomeruli and arterioles synthesize not only the vasodilatory prostaglandins PGE2 and PGI2, but also the vasoconstrictor, thromboxane A2. The primary renal cortical actions of these prostaglandins are renal vasodilatation and maintenance of GFR (PGE2 and PGI2) or renal vasoconstriction and reduction of GFR (thromboxane A2). Vasodilatory renal prostaglandins are relatively unimportant under normal circumstances but play a modulatory role after ischemia or in the presence of increased concentrations of vasoconstrictor substances such as angiotensin II (ANG II), vasopressin or norepinephrine. ANG II and vasopressin stimulate the synthesis of PGE2 in rat glomerular epithelial and mesangial cells maintained in cell culture. These stimulatory actions of constrictor peptides are dependent upon calcium entry into the cells since removal of extracellular calcium or co-incubation with verapamil or nifedipine block the prostaglandin stimulatory capacity of ANG II or vasopressin. In vivo indomethacin potentiates the actions of ANG II on the kidney, particularly the reduction of RBF and GFR. Isolated rat glomeruli contract in response to ANG II and this contractile effect, which reflects reduction in glomerular filtration surface area, can be potentiated by cyclooxygenase blockade. Conversely, arachidonic acid reduces the glomerular contractile effect of ANG II. The importance of renal prostaglandins in support of RBF and GFR has been studied in dogs after chronic bile duct ligation (CBDL). CBDL dogs have significant increase in renal PGE2 and PGI2 which maintain RBF and GFR since cyclo-oxygenase inhibition resulted in a 50% decrease in both RBF and GFR. Indomethacin, ibuprofen, naproxen, and sulindac sulfide had comparable effects. The pro-drug, sulindac sulfoxide, was tested in normal volunteers and found to spare renal prostaglandin synthesis whereas indomethacin reduced renal synthesis of PGE2 and PGF2 alpha by more than 50%. In vitro, sulindac sulfide is a potent inhibitor of renal prostaglandin synthesis by kidney cells in culture. It is, therefore, concluded that renal prostaglandins play an important vasoregulatory role. Furthermore, sulindac sulfoxide may spare renal cyclo-oxygenase and thereby preserve renal function.
 ...
PMID:Mechanisms of the nephrotoxicity of non-steroidal anti-inflammatory drugs. 659 99

Swiss mouse 3T3 fibroblasts were grown in tissue culture, fixed with lysine-paraformaldehyde-periodate solutions containing 0 to 0.1% Tween 20, and then stained for cyclooxygenase antigenicity using rabbit anti-cyclooxygenase IgG in the peroxidase anti-peroxidase procedure. When examined by light microscopy, those cells fixed in the presence of 0.03 to 0.1% Tween 20 exhibited staining throughout the cytoplasm and around the nucleus but not on the cell surface. No staining occurred when either preimmune IgG or anti-cyclooxygenase IgG adsorbed with purified enzyme was substituted for the immune IgG. Electron microscopic examination of cells treated with fixative containing 0.05% Tween 20 and then stained for cyclooxygenase antigenicity revealed electron-dense deposits on the endoplasmic reticulum and nuclear membrane but not the mitochondrial or plasma membranes. No staining was seen in cells treated with control sera. Agents such as angiotensin II, bradykinin, antidiuretic hormone, and thrombin interact, apparently with the 3T3 cell surface to cause a release of arachidonic acid and prostaglandin E2 formation (Pong, S.S., Hong, S. L., and Levine, L. (1977) J. Biol. Chem. 252, 1408-1413). Our results establish that conversion of arachidonic acid to the prostaglandin endoperoxide precursor of PGE2 actually takes place on the endoplasmic reticulum and the nuclear envelope.
 ...
PMID:Subcellular localization of prostaglandin-forming cyclooxygenase in Swiss mouse 3T3 fibroblasts by electron microscopic immunocytochemistry. 676 26

1 The relative importance of the effect of prostaglandins on renal sodium and water reabsorption was assessed in rats. 2 Clearance experiments were performed on 24 anaesthetized rats divided into 3 groups. Each group was infused throughout either with Ringer solution at 9 ml/h (Protocol I), or at 3 ml/h (Protocol II) or with hypotonic fluid at 5 ml/h (Protocol III). Clearance periods were performed before and after intravenous injection of indomethacin (5 mg/kg) and then of aspirin (20 mg/kg). The natriuretic response to different degrees of volume expansion was not modified during the action of the inhibitors. 3 When baseline urine osmolality (Uosm) was high (Protocol II) no further increase occurred in the presence of prostaglandin inhibition. Conversely, Uosm rose from 771 +/- 134 to 1356 +/- 414 and from 575 +/- 245 to 841 +/- 407 mosm/kg (P less than 0.05) in Protocol I and Protocol III respectively, when antidiuretic hormone secretion was inhibited by the higher degree of volume expansion. 4 There was a significant correlation between the change in urine flow rate induced by cyclooxygenase inhibitors and the attendant variations in Na excretion, r = 0.42, n = 41, P less than 0.01. 5 Thus, prostaglandins affect Na loss during saline load as a side effect of their action on water permeability. They could play an important role in volume depletion by counterbalancing the large secretion rate of renal vasoconstrictors.
 ...
PMID:Experimental dissociation of the effects of prostaglandins on renal sodium and water reabsorption by cyclo-oxygenase inhibitors in the rat. 680 89

The present studies examined whether vasopressin increases prostaglandin biosynthesis in isolated rabbit cortical collecting tubules (CCT) and whether endogenous prostaglandin biosynthesis plays a role in modulating the response of this nephron segment to vasopressin. Three groups of studies were performed. In the first group, CCT and proximal straight tubules (PST) were incubated with [(3)H]arachidonic acid, and metabolites were separated and identified using silica gel thin-layer chromatography. CCT were capable of producing all of the major prostaglandins (PG) (PGE(2) > thromboxane B(2)[TxB(2)] > PGF(2alpha) > PGI(2)). PST produced significantly lesser quantities of these lipids. In the second group, radiolabeled arachidonic acid was incorporated into the phospholipid pool of both CCT and PST, vasopressin was added to the incubation medium, and metabolities were separated and identified as above. Vasopressin stimulated the release of all of the major prostaglandins in CCT but had no effect on PST. PGE release into the incubation medium, as assessed by a radioreceptor assay, increased 108%, and a vasopressin analogue, 1-desamino-8-d-arginine vasopressin, had a quantitatively similar effect. In the third group, a submaximal dose of vasopressin was administered to isolated, perfused CCT studied in the presence and absence of indomethacin to assess whether endogenous prostaglandins play a role in modulating the antidiuretic response to vasopressin. Studies were performed in rabbits on a normal diet and in desoxycorticosterone acetate (DOCA)- or KCl-loaded animals. In the state of mineralocorticoid excess, basal prostaglandin synthesis was 63% lower, and vasopressin-stimulated prostaglandin synthesis 76% lower, than the synthesis observed in rabbits on a normal diet. Cyclooxygenase inhibition exposed a significant hydroosmotic response to a submaximal dose of vasopressin in CCT from DOCA- or KCl-loaded animals. With arachidonic acid in the bath, the same dose of vasopressin failed to elicit a hydroosmotic response in CCT from rabbits on a normal diet even in the presence of a cyclooxygenase inhibitor. However, removal of exogenous arachidonic acid, with a consequently lower rate of prostaglandin synthesis, allowed the cyclooxygenase inhibitor to enhance the hydroosmotic response to vasopressin in these tubules.We conclude from these studies that the rabbit CCT has the capacity to synthesize all of the major prostaglandins and that the rate of synthesis of these lipids is enhanced by vasopessin. Prostaglandin synthesis by the CCT is postulated to modulate the antidiuretic action of vasopressin via a closed feedback loop. The effectiveness of this feedback regulation is dependent upon the mineralocorticoid status of the animal, which determines the level of basal and vasopressin-stimulated prostaglandin synthesis by the CCT.
 ...
PMID:Regulation of vasopressin action by prostaglandins. Evidence for prostaglandin synthesis in the rabbit cortical collecting tubule. 717 90

Responses to angiotensin II, bradykinin and arginine vasopressin were compared in helical strips of canine pulmonary arteries and veins. Angiotensin II contracted the artery but relaxed the vein strip. The artery contraction was augmented by indomethacin and aspirin and was abolished by losartan. The vein relaxation was not affected by endothelium denudation but was abolished by the cyclooxygenase inhibitors, a prostaglandin I2 synthase inhibitor and losartan. The bradykinin-induced artery relaxation was inhibited by endothelium denudation, NG-nitro-L-arginine (L-NA) or indomethacin and abolished by their combined treatment. The vein relaxation produced by bradykinin was endothelium-independent and was abolished by indomethacin. Vasopressin produced a slight relaxation in the arteries, which was abolished by endothelium denudation and L-NA. The vein relaxation produced by vasopressin was abolished by endothelium denudation and combined treatment with L-NA and indomethacin. It may be concluded that (1) activation of angiotensin AT1 receptor subtype in smooth muscle produces contraction and also relaxation due to prostaglandin I2 release; the former predominates over the latter in the artery, whereas only the latter is operative in the vein, (2) the bradykinin-induced relaxation is due to nitric oxide (NO) from the endothelium and prostaglandin I2 from subendothelial tissues in the artery and solely to prostaglandin I2 in the veins, and (3) the vasopressin-induced relaxation is mediated by endothelial NO in the artery, and NO and prostaglandin I2 in the vein.
 ...
PMID:Comparison of responses of canine pulmonary artery and vein to angiotensin II, bradykinin and vasopressin. 749 82

Parathyroid hormone (PTH) has been implicated in hypertension, but PTH infusion results in vasodilation. PTH activates adenylate cyclase in vascular smooth muscle, but little is known about the factors that regulate PTH receptor/adenylate cyclase coupling in vascular cells. To characterize hormone-receptor signaling, we measured cyclic AMP levels in rat arterial smooth muscle cells in culture exposed to PTH (bovine 1-34). PTH yielded time- and concentration-dependent increases in cyclic AMP levels. Compared with isoproterenol, PTH was more potent, with a threshold at 2 x 10(-9) versus 5 x 10(-8) mol/L and half maximal responses at 10(-8) versus 2.4 x 10(-7) mol/L. PTH-induced increases in cyclic AMP were independent of extracellular calcium, cyclooxygenase metabolites, phospholipase C, and protein kinase C because PTH-induced increases in cyclic AMP were not prevented by variations in extracellular calcium, indomethacin, angiotensin II, vasopressin, and protein kinase C activators or inhibitors. PTH/adenylate cyclase coupling was G protein-dependent because increases in cyclic AMP were prevented by preincubation with cholera toxin but not with pertussis toxin. Prolonged exposure to PTH resulted in time- and concentration-dependent homologous desensitization of cyclic AMP responses. Desensitization occurred proximal to G protein/adenylate cyclase because after prolonged PTH, responses to forskolin and cholera toxin remained intact. Desensitization was independent of protein kinase A and receptor sequestration because cyclic AMP responses remained after prolonged exposure to forskolin and pretreatment with phenylarsine oxide, colchicine, and cytochalasin D. We conclude that in vascular smooth muscle cells, PTH is coupled to adenylate cyclase through a cholera toxin-sensitive G protein.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Parathyroid hormone/adenylate cyclase coupling in vascular smooth muscle cells. 751 68

We examined the activities of bradykinin, substance P, and vasopressin in isolated human cerebral arteries to better understand humoral control of cerebrovascular tone. Basilar and middle cerebral arteries were isolated from human cadavers during autopsy, and isometric tension was measured in helical strips of the arteries. Both bradykinin and substance P relaxed strips of both arteries precontracted with prostaglandin F2 alpha to similar extents. The relaxations induced by both peptides were abolished by removal of the vascular endothelium and were markedly reduced by pretreatment with NG-nitro-L-arginine, an inhibitor of endothelium-derived relaxing factor. Treatment with indomethacin, a cyclooxygenase inhibitor, did not attenuate the relaxations. These results indicate that the responses of human cerebral arteries to bradykinin and substance P are mediated by endothelium-derived relaxing factor. In contrast, vasopressin primarily produced endothelium-independent contractions in human cerebral arteries. Contractions of basilar arteries induced by vasopressin were much less than those of middle cerebral arteries. Two of eighteen basilar arteries, but none of the middle cerebral arteries, responded to vasopressin with endothelium-dependent relaxation. This suggests that the function of vasopressin receptors differs in basilar and middle cerebral arteries.
 ...
PMID:Human basilar and middle cerebral arteries exhibit endothelium-dependent responses to peptides. 752 7

In order to investigate the functional role of endothelium and vasoeffector mechanism in cerebrovascular responses to neuropeptides, the stainless steel cannula inserting method was applied to examine the responses to intraluminally-applied bradykinin, substance P and vasopressin in isolated and perfused canine basilar arteries. In control vessels with intact endothelium, each neuropeptide induced a monophasic dilation at lower doses, and a biphasic response, i.e., an initial dilation followed by a secondary constriction, at higher doses. The dilation was significantly reduced and the constriction was significantly enhanced, while the dilation to papaverine was not modified by endothelial removal with intraluminal saponin. The same tendency was observed in the responses after extraluminal treatment with oxyhaemoglobin. The monophasic constrictions to prostaglandin F2 alpha and potassium chloride were significantly potentiated by the endothelial removal. The augmented constrictions to the neuropeptides were significantly diminished by indomethacin (a cyclooxygenase inhibitor), OKY-046 (a thromboxane synthetase inhibitor) and nimodipine (a dihydropyridine calcium antagonist), but not by AA-861 (a lipoxygenase inhibitor). These results suggest that the neuropeptide causes an endothelium-dependent dilation and a constriction of smooth muscles, and that the enhanced constriction might be relevant in part with thromboxane A2, linked with calcium influx into smooth muscle cells in cerebral arteries.
 ...
PMID:Vasoconstrictor mechanism of neuropeptides augmented after endothelial removal in isolated, perfused canine basilar arteries. 754 80

The present study was designed to investigate the possible role of endothelium-derived vasodilators, nitric oxide and prostaglandins, in the regulation of blood pressure during the presence and absence of the major pressor systems. Conscious rats were infused with a cocktail of inhibitors of the sympathetic nervous system, renin-angiotensin system, and V1 vascular receptor to vasopressin (achieved with hexamethonium, captopril, phentolamine, propranolol, and the V1 vasopressin (AVP) antagonist des-(CH2)5Tyr(Me)-AVP). The cocktail of vasoconstrictor inhibitors induced a marked fall of mean arterial pressure (MAP) from 109 +/- 2 to 52 +/- 2 mmHg (1 mmHg = 133.3 Pa) (n = 24). In animals with blockade, the specific inhibitor of nitric oxide synthesis, NG-nitro-L-arginine methyl ester (L-NAME), induced a significant increase of MAP from 51 +/- 1 to 84 +/- 2 mmHg (n = 6). In the presence of indomethacin, a cyclooxygenase inhibitor, the pressor response to L-NAME was from 52 +/- 2 to 126 +/- 4 mmHg (n = 6). Neither indomethacin (n = 6) nor vehicle (n = 6) alone altered MAP. In intact animals without blockade, L-NAME caused a similar increase of MAP when it was injected alone (from 107 +/- 3 to 144 +/- 4 mmHg, n = 7) or with indomethacin (from 113 +/- 3 to 144 +/- 3, n = 6). Indomethacin alone (n = 8) did not change MAP. In conclusion, in the absence of the major pressor systems, the pressor effect of the inhibition of the production of endogenous nitric oxide and vasodilator prostanoid synthesis appears to be synergistic. These results suggest that these two endogenous vasodilators are involved in the maintenance of blood pressure.
 ...
PMID:Role of nitric oxide and prostaglandins in the regulation of blood pressure in conscious rats. 758 39

The aim of the study was to investigate to what extent inhibition of nitric oxide (NO) formation, cyclooxygenase and converting enzyme activities and vasopressin V1 receptors blockade affects the cardiovascular system in conscious, freely moving normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The experiments were performed on 33 WKY and on 33 SHR. In series 1 (8 WKY and 8 SHR) animals received bolus injection of N omega-nitro-L-arginine - NLA (10 mg/kg), in series 2 (6 WKY and 6 SHR) bolus injection of indomethacin (10 mg/kg). In series 3 (8 WKY and 8 SHR) the animals received captopril as initial bolus (1 mg/kg) followed by constant infusion (1 mg/kg/min), in series 4 (11 WKY and 11 SHR) vasopressin V1 receptor antagonist 1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine-vasopressin (MeCAAVP) was infused (1.52 micrograms/kg/min). In series 1 in WKY NLA elicited a long-lasting, significant increase in mean blood pressure (max 46 +/- 3 mmHg at 40 min). In SHR mean blood pressure raises were not significant (max 22 +/- 6 mmHg). In series 2, both in WKY and SHR, indomethacin elicited only transient, nonsignificant increases in mean blood pressure. In series 3, the mean blood pressure fall during the captopril infusion was more pronounced in SHR than in WKY (45 +/- 2 mmHg vs 13 +/- 2 mmHg respectively). In series 4 vasopressin V1 receptor blockade caused a nonsignificant fall in mean blood pressure, both in WKY and SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Blood pressure responses to substances interfering with nitric oxide formation, cyclooxygenase and converting enzyme activities and vasopressin V1 receptors blockade in conscious spontaneously hypertensive and normotensive rats. 800 Apr 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>