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)

Desmopressin (DDAVP), a synthetic analogue of vasopressin, has been shown to improve the bleeding time in patients with cirrhosis. The duration of this effect and the hemodynamic changes associated with DDAVP have not been studied so far. To evaluate these issues, 14 cirrhotics with portal hypertension were studied in basal conditions and after DDAVP (0.3 uk/kg). In 8 patients, hemostatic tests were done at basal conditions and 1, 3, 6 and 24 hs after drug administration. In the remaining 6 patients, mean arterial pressure, cardiac output, portal and femoral blood flows were evaluated. Hemodynamic parameters were measured by Doppler ultrasound. DDVP caused a marked decrease in bleeding time at 1, 3, 6 and 24 hs (14 +/- 9 vs 8 +/- 3, 7 +/- 4, 6 +/- 4 and 8 +/- 4 min, respectively); the decrease was maximal and statistically significant at 6 hs (55 +/- 15%, p < 0.02) after DDAVP infusion. Bleeding time reduction was observed in every patient studied. In the hemodynamic study, DDAVP caused a mild but significant decrease in mean arterial pressure (12 +/- 8%, p < 0.05); no significant changes were observed in the rest of hemodynamic parameters studied. These findings show that DDAVP can be used to shorten the bleeding time for a period of at least 24 hs in patients with cirrhosis, without deleterious hemodynamic effects. This beneficial effect may be of potential relevance in the medical management of patients with chronic liver diseases.
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PMID:Hemostatic and hemodynamic effects of vasopressin analogue DDAVP in patients with cirrhosis. 933 35

Desmopressin (1-desamino-[DArg8]vasopressin, is a synthetic analogue of the neurohypophyseal peptide hormone vasopressin which has high antidiuretic and antibleeding potency. The structure of desmopressin has been determined in aqueous solution by two-dimensional NMR techniques and molecular dynamics simulations. Both standard and time-averaged distance restraints were used in structure calculations because of the inherent flexibility in small peptides. 21 models calculated with standard restraints were compared with structures refined with time-averaged distance restraints and were found to be good representatives of the conformational ensemble of desmopressin. The macrocyclic ring forms an inverse gamma-turn centered around Gln4. Residues 1 and 2, the disulphide bridge and the three-residue acyclic tail were found to be flexible in solution. Residues 4-6 in the ensemble of calculated structures contain essentially the same backbone conformation as in the crystal structure of pressinoic acid, the cyclic moiety of vasopressin, whereas residues 2-6 superimpose on the NMR-derived conformation of oxytocin bound to neurophysin. The results presented in this work suggest that, in addition to the differences in sequence between desmopressin and vasopressin, differences in conformational and dynamic properties between the two compounds explain their pharmacological differences.
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PMID:Conformation of desmopressin, an analogue of the peptide hormone vasopressin, in aqueous solution as determined by NMR spectroscopy. 954 58

To examine the role of vasopressin V1 and V2 receptors, nitric oxide and prostanoids in the coronary vascular effects of [Arg8]vasopressin, coronary blood flow was measured with an electromagnetic flow transducer placed around the left circumflex (23 goats) or anterior descending (11 goats) coronary artery and vasopressin (0.03-1 microg) was intracoronarily injected in 34 anesthetized, open-chest goats. Basal mean values for coronary blood flow, mean systemic arterial pressure and heart rate, were 34 +/- 2.38 ml/min, 89 +/- 3.34 mmHg and 80 +/- 3.06 beats/min, respectively. Vasopressin produced dose-dependent decreases in coronary blood flow and the maximal reduction of this flow, attained with 1 microg of vasopressin, was 14 +/- 1.49 ml/min (42 +/- 2.64% of basal flow) (P < 0.01). Desmopressin (0.03-1 microg; 8 goats) did not affect significantly coronary blood flow. The intracoronary infusion of the antagonist for vasopressin V1 receptors d(CH2)5Tyr (Me) arginine vasopressin (2 microg/min per kg, 6 animals) significantly diminished the effects of vasopressin on coronary blood flow (the effects of 1 microg of vasopressin were reduced by 28%, P < 0.05). The mixed antagonist for vasopressin V1 and V2 receptors desGly-d(CH2)5-D-Tyr(Et)Val arginine vasopressin (0.2, 0.7 and 2 microg/min per kg, 9 animals) decreased in a dose-dependent manner the effects of vasopressin on coronary blood flow (the effects of 1 microg of vasopressin were decreased by 61% with 2 microg/min per kg, P < 0.01). Intracoronary infusion of saline (vehicle, 3 goats) did not change the effects of vasopressin on coronary blood flow. Intravenous administration of the inhibitor of nitric oxide synthesis N-omega-nitro-L-arginine methyl ester (L-NAME, 47 mg/kg, 9 animals) decreased resting coronary blood flow by 10% (P < 0.01) and augmented mean systemic arterial pressure by 20% (P < 0.01), without changing heart rate. During this treatment the reduction in coronary blood flow produced by vasopressin was higher than under control (the effects of 1 microg of vasopressin were increased by 28%, P < 0.01). Intravenous administration of the inhibitor of cyclooxygenase, meclofenamate (5 mg/kg, 7 animals), neither modified resting coronary blood flow, arterial pressure and heart rate nor the effects of vasopressin on this flow. These data indicate that vasopressin produces marked coronary vasoconstriction and suggest that: (a) it may be mediated by vasopressin V1 receptors, without involvement of vasopressin V2 receptors, (b) it is probably inhibited by nitric oxide under normal conditions and (c) it may be not modulated by prostanoids.
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PMID:Coronary vasoconstriction produced by vasopressin in anesthetized goats. Role of vasopressin V1 and V2 receptors and nitric oxide. 954 90

Meningitis is often associated with hyponatremia due to inappropriate secretion of antidiuretic hormone, and diabetes insipidus is associated with bacterial meningitis. This article describes a patient with acquired immunodeficiency syndrome who experienced recurrent episodes of central diabetes insipidus in association with recurrent fungal meningitis. Desmopressin was effective in controlling the polyuria until the episodes of meningitis resolved.
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PMID:Recurrent central diabetes insipidus secondary to cryptococcal meningitis. 958 72

In isolated dog posterior ciliary arteries contracted with prostaglandin F2alpha, desmopressin (10(-10) to 10(-8) M), a vasopressin V2 receptor agonist, produced a concentration-related relaxation, which was reversed to a contraction by removal of the endothelium. Desmopressin was approximately 1/100 as potent as arginine vasopressin. Treatment with NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, reversed the desmopressin-induced relaxation to a contraction and the addition of L-arginine restored the relaxation. SR49059 ((2S)1-[(2 R3S)-(5-chloro-3-(2-chlorophenyl)-1-(3,4-methoxybenzene-s ulfony)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-car boxamide), a selective vasopressin V1 receptor antagonist, suppressed the relaxation. In endothelium-denuded arteries, desmopressin-induced contractions were also inhibited by SR49059. It is concluded that desmopressin, although much less potent than vasopressin, relaxes ciliary arteries via a mediation of NO synthesized from L-arginine in the endothelium. Vasopressin V1-receptor Subtypes appear to be involved in the desmopressin-induced relaxation and contraction.
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PMID:Desmopressin-induced dog ciliary artery relaxation. 960 Jun 55

Arginine vasotocin (AVT) is present in the neurohypophysis of all nonmammalian vertebrates and it appears to be the antecedent of the neurohypophysial nonapeptide hormones. Relatively little is known about AVT receptors in lower vertebrates, especially fish, and the present study was designed to examine AVT receptor interactions in trout vascular and nonvascular smooth muscle in vitro. AVT produced dose-dependent contraction of isolated rings from celiacomesenteric, coronary, and efferent branchial arteries, ventral aorta, anterior cardinal vein, and strips of ductus Cuvier. The greatest efficacy (magnitude of contraction per unit tissue weight) and sensitivity (effective concentration for half-maximal response, EC50) to AVT was found in the efferent bronchial artery (EBA) and its receptors were characterized further. Other neurohypophysial peptides, including arginine vasopressin (AVP), lysine vasopressin (LVP), isotocin (IST), and oxytocin (OXY), contracted EBA with an efficacy order of (most to least) AVT = AVP = OXY > LVP > IST and a sensitivity order of AVT > OXY >/= AVP > IST > LVP. Neither Desmopressin, an AVP V2-receptor agonist, nor the AVP ring fragment, AVP4-9, contracted EBA nor did they inhibit AVT contraction. Pretreatment of EBA rings with the selective AVP V1-receptor antagonists (deamino-Pen1, O-Me-Tyr2, Arg8-vasopressin and deamino-Pen1, Val4, Arg8-vasopressin), the selective V2-receptor antagonist (adamantaneacetyl1, O-Et-D-Tyr0, Val4, aminobutyryl6, Arg8,9-vasopressin), or the combined V1-oxytocin receptor antagonist (d(CH2)5[Tyr(Me)2, Orn8-AVT]) competitively inhibited AVT contractions without affecting AVT efficacy. Receptor affinity constants (pA2) determined by Schild analysis were in the range of 6.8-7.3, with slightly higher constants for the AVP V1-/oxytocin receptor antagonists than for the selective V2-receptor antagonist. Endothelium removal had no effect on EBA sensitivity to AVT. EBA rings were an order of magnitude more sensitive to AVT than nonvascular gastrointestinal and urinary bladder smooth muscle rings or strips. However, AVT (10(-7) M) was as efficacious as acetylcholine (10(-5) M) in gastrointestinal, gallbladder, and urinary bladder smooth muscle. It is concluded that trout EBA possess an AVT smooth muscle receptor that shares a similar pharmacological profile with the mammalian vascular AVP V1a-receptor and the OXY-receptor, but it is distinct from the previously reported gill epithelial cell receptor.
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PMID:Pharmacological characterization of arginine vasotocin vascular smooth muscle receptors in the trout (Oncorhynchus mykiss) in vitro. 1009 57

In order to analyse the effects of arginine-vasopressin on the vascular contraction to sympathetic nerve stimulation during cooling, the isometric response of isolated, 2-mm segments of the rabbit central ear (cutaneous) artery to electrical field stimulation (1-8 Hz) was recorded at 37 and 30 degrees C. Electrical stimulation (37 degrees C) produced frequency-dependent arterial contraction, which was reduced at 30 degrees C and potentiated by vasopressin (10 pM, 100 pM and 1 nM). This potentiation was greater at 30 than at 37 degrees C and was abolished at both temperatures by the antagonist of vasopressin V1 receptors d(CH2)5 Tyr(Me)AVP (100 nM). Desmopressin (1 microM) did not affect the response to electrical stimulation. At 37 degrees C, the vasopressin-induced potentiation was abolished by the purinoceptor antagonist PPADS (30 microM), increased by phentolamine (1 microM) or prazosin (1 microM) and not modified by yohimbine (1 microM), whilst at 30 degrees C, the potentiation was reduced by phentolamine, yohimbine or PPADS, and was not modified by prazosin. The Ca2+-channel blockers, verapamil (10 microM) and NiCl2 (1 mM), abolished the potentiating effects of vasopressin at 37 degrees C whilst verapamil reduced and NiCl2 abolished this potentiation at 30 degrees C. The inhibitor of nitric oxide synthesis, L-NOARG (100 microM), or endothelium removal did not modify the potentiation by vasopressin at 37 and 30 degrees C. Vasopressin also increased the arterial contraction to the alpha2-adrenoceptor agonist BHT-920 (10 microM) and to ATP (2 mM) at 30 and 37 degrees C, but it did not modify the contraction to noradrenaline (1 microM) at either temperature. These results suggest that in cutaneous (ear) arteries, vasopressin potentiaties sympathetic vasoconstriction to a greater extent at 30 than at 37 degrees C by activating vasopressin V1 receptors and Ca2+ channels at both temperatures. At 37 degrees C, the potentiation appears related to activation of the purinoceptor component and, at 30 degrees C, to activation of both purinoceptor and alpha2-adrenoceptor components of the sympathetic response.
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PMID:Effects of vasopressin on the sympathetic contraction of rabbit ear artery during cooling. 1018 92

Desmopressin [1-(mercaptopropanoic acid)-8-D-arginine vasopressin; dDAVP] is a vasopressin analogue with a selective antidiuretic effect. The oral bioavailability of desmopressin is limited due both to its high hydrophilicity leading to a low intestinal permeability and to low enzymatic stability. The degradation of desmopressin was investigated in aqueous buffer solutions (pH 6.00-9.00) containing the enzyme alpha-chymotrypsin at a concentration of 0.50 mg/ml at 37 degrees C. The degradation of desmopressin was also studied in solutions containing alpha-chymotrypsin in the concentration range 0.10-1.00 mg/ml (pH 7.40 and 37 degrees C). The rate of degradation was shown to be highly dependent on both enzyme concentration and pH. Maximal alpha-chymotrypsin activity was observed in the pH range 7.40-8.00. It was observed that phenylalanine was formed during the degradation of desmopressin. Phenylalanine was formed in the amount of 20% in 120 min. In the same time period 95% of desmopressin was degraded. The formation of phenylalanine can be explained from the substrate specificity of alpha-chymotrypsin. Cyclodextrins are known to stabilize drugs including peptides against both chemical and enzymatic degradation. In this study it was shown that hydroxypropyl cyclodextrins (alpha, beta and gamma) stabilized desmopressin against alpha-chymotrypsin-catalyzed degradation. The stabilization was by a factor of 3, 9 and 8 at the concentration 12.5% (w/v) for hydroxypropyl-alpha-cyclodextrin, hydroxylpropyl-beta-cyclodextrin and hydroxypropyl-gamma-cyclodextrin.
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PMID:alpha-Chymotrypsin-catalyzed degradation of desmopressin (dDAVP): influence of pH, concentration and various cyclodextrins. 1020 42

Desmopressin responders tend to have a large volume of urine production at night, in contrast to desmopressin refractory patients who often produce normal volumes of urine. Controls and adolescent/adult primary monosymptomatic nocturnal enuretics were included in a study measuring urine volume and plasma vasopressin levels before and during a 24-hour water deprivation test. The results indicate a significantly higher urine production in desmopressin responders when compared with controls and non-responders. Before fluid deprivation, only the nocturnal polyuric patients showed a urine osmolality significantly lower than that of controls and desmopressin non-responders. A significant decrease in the clearance of osmols was evident in the desmopressin refractory group from day to night. All three groups showed a significant increase in plasma vasopressin during fluid deprivation, with polyuric, desmopressin-responding patients showing a lower increase that the non-responders and controls. Plasma vasopressin levels were normal in adolescent and adult enuretics regardless of their response to desmopressin. Moreover, response to fluid deprivation in both polyuric and enuretic patients resulted in a significant decrease in urine output from the first to the second night.
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PMID:Fluid deprivation in enuresis--effect on urine output and plasma arginine vasopressin. 1057 94

Desmopressin (DDAVP), a synthetic analogue of vasopressin has been successfully used in the treatment of type I von Willebrand's disease (VWD), mild factor VIII (FVIII) deficiency and intrinsic platelet function defects (PFDs) for almost three decades. However, there is limited published data documenting its efficacy and the reliability of circulating plasma FVIII:C as a surrogate marker of response to therapy in VWD. We report the haemostatic response to DDAVP in 133 consecutive patients (91 type I VWD, 20 mild FVIII deficiency and 22 PFDs). Minimal therapeutic response to DDAVP (0.3 microg/kg) was defined by normalization 30 min post- infusion of bleeding time for PFDs, factor VIII:C (FVIII:C) for mild haemophilia A, and von Willebrand factor antigen (VWF:Ag), von Willebrand factor functional activity (VWF:Ac) and FVIII:C for VWD. Nine out of 91 (10%) VWD patients failed to achieve minimal therapeutic response to DDAVP; plasma FVIII:C levels were an unreliable surrogate marker of DDAVP response as 6 out of 9 (67%) of these patients had normal post-infusion FVIII:C levels. Five out of the 20 (25%) patients with mild FVIII deficiency and 5 out of 22 (23%) patients with PFDs failed to achieve a minimal therapeutic response to DDAVP. DDAVP is an effective therapy in the majority of patients with type I VWD, PFDs and mild FVIII deficiency. The significant failure rate associated with this therapy supports the recent recommendations that response should be assessed in all patients at the time of diagnosis. FVIII:C is an unreliable guide of response to DDAVP in patients with VWD and therefore VWF:Ag and VWF:Ac should also be assessed. Failure to demonstrate the response of VWF:Ag, VWF:Ac and FVIII:C to DDAVP in patients with VWD is likely to increase the risk of haemorrhagic complications in patients with bleeding episodes or who are undergoing surgery.
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PMID:Desmopressin: therapeutic limitations in children and adults with inherited coagulation disorders. 1092 43


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