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)

The role of pituitary vasopressin (antidiuretic hormone--ADH) in the formation and dynamics of aqueous humour was studied in rabbits employing different techniques. Using isolated ciliary body preparations the changes in transepithelial short-circuit current were measured, and natural vasopressin and Lys8-vasopressin were found to increase the transepithelial short-circuit current at concentrations less than 10 muU/ml (i.e. within the physiological range), indicating increased sodium transport across the ciliary epithelium. In another series of experiments with intact rabbits given an ethanol load to suppress endogenous ADH, administration of exogenous vasopressin raised the intraocular pressure, and a similar effect was observed when endogenous ADH production was stimulated with nicotine. Direct measurements of outflow showed that vasopressin was without effect when given intravenously and that the only effect when given intracamerally was to increase the facility which would tend to lower rather than raise the intraocular pressure. Finally, the intra-arterial and intravenous effects of vasopressin on circulation in the iris and on the intraocular and systemic arterial pressures were studied. Local effects on the vascular bed in the eye and changes in systemic blood pressure were observed only at rates of administration well in excess of the physiological range for endogenous vasopressin production. It is concluded that, at physiological levels, antidiuretic hormone can stimulate active sodium transport into the eye thereby tending to raise the intraocular pressure, and it is suggested that this may act as a homeostatic regulating mechanism limiting changes in the rate of formation of aqueous humour and in intraocular pressure which might otherwise result from diurnal variations in the state of body hydration. This also offers some explanation for the ocular hypotensive action of ethanol.
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PMID:Role of pituitary vasopressin in the formation and dynamics of aqueous humour. 28 4

A detailed review of the hormonal effects on intraocular pressure is presented. There is evidence that corticotropin, vasopressin, thyroxin, insulin, glucocorticoids and mineralocorticoids may play a role in the physiologic regulation of intraocular pressure. Growth hormone, melanocyte stimulating hormone, progesterone, estrogen, chorionic gonadotropin and relaxin may influence intraocular pressure when administered in pharmacologic doses. Whether the key to understanding primary open-angle glaucoma lies in recognizing abnormal endocrine mechanisms, especially involving glucocorticoids, remains unclear at the present time.
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PMID:Hormonal regulation of intraocular pressure. 41 3

Intravenous desmopressin, a synthetic antidiuretic hormone, resulted in a dose-dependent increase in intraocular pressure (IOP) in rabbits. IOP was increased 3.6 +/- 0.8 mm Hg 6 hr following injection of desmopressin 200 mUnits/kg with the increase lasting over 10 hr. IOP returned to baseline 24 hr after the injection. Systemic blood pressure, plasma osmolarity and arterial blood gases were not altered by desmopressin. The increased IOP was not associated with alterations in measured outflow facility or episcleral venous pressure. Five hours after desmopressin injection, calculated aqueous humor flow was increased approximately 57%. Aqueous humor ascorbate measurements for calculation of flow to diffusion ratios and anterior chamber fluorophotometry also were consistent with an increased rate of aqueous humor formation as the mechanism for the IOP elevation. Desmopressin administration did not increase aqueous humor protein or aqueous humor cyclic AMP concentration. Systemic pretreatment with indomethacin only partially blocked the IOP increase. Systemic pretreatment with demeclocycline completely blocked the desmopressin-induced increase in IOP.
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PMID:Effects of systemic desmopressin on aqueous humor dynamics in rabbits. 283 Feb 1

Rabbits subjected to free-floating body immersion demonstrated decreases in intraocular pressure followed by later increases. These intraocular pressure alterations were associated with parallel changes in aqueous humor production. Episcleral venous pressure was elevated during immersion but outflow facility was unaltered. The decrease in intraocular pressure could be partially blocked by pretreatment with vasopressin or desoxycorticosterone acetate. In cross-circulation studies between an immersed and non-immersed rabbit, a decrease in intraocular pressure was observed in both animals. This observation further supported the involvement of humoral factors in the body-immersion induced intraocular pressure response.
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PMID:The effects of body immersion on aqueous humor dynamics in rabbits. 670 46

The effects of atrial natriuretic peptide (ANP), vasopressin (AVP) and angiotensin (ANG) on blood and intraocular pressures of pentobarbital anesthetized rats were evaluated following intravenous, intracerebroventricular or anterior chamber routes of administration. Central injections did not affect intraocular pressure. Equipressor intravenous infusions of ANG raised, whereas AVP decreased, intraocular pressure. Direct infusions of a balanced salt solution (0.175 microliter/min) raised intraocular pressure between 30 and 60 min. Adding ANG or ANP slightly reduced this solvent effect but AVP was markedly inhibitory. An AVP-V1 receptor antagonist reversed the blunting of the solvent-induced rise by the peptide, indicating receptor specificity. Acetazolamide pretreatment lowered intraocular pressure, but the solvent-induced rise in intraocular pressure and inhibition by AVP still occurred without altering the temporal pattern. Thus, these effects appear unrelated to aqueous humor synthesis rate. The data support the possibility of intraocular pressure regulation by peptides acting from the blood and aqueous humor.
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PMID:Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats. 858 37

Head-down tilt or infusions of a balanced salt solution into the anterior chamber of the eye raise intraocular pressure. We measured intraocular pressure directly in adult male Sprague-Dawley rats, anesthetized with pentobarbital, and subjected to 45 degrees head-down tilt alone, tilt with an anterior chamber infusion (0.087 microliter min-1), or tilt with an infusion containing arginine vasopressin. The intraocular pressure of the three groups differed during the 1 hr tilt and recovery periods. In the case of tilt alone, intraocular pressure quickly reached a peak after tilting, partially decreased during the tilt period, recovered to baseline immediately after tilt, then a secondary rise occurred. Combined infusion and tilt caused a slower rise to peak intraocular pressure, and only a partial recovery occurred during the 1 hr recovery period. Combined vasopressin infusion and tilt caused a gradual rise in intraocular pressure of a lesser magnitude than the other groups, followed by a rapid recovery to baseline pressure and no secondary rise. Systemic arterial pressure was stable within and between the groups. The underlying mechanism for these differing response patterns is unknown. However, some evidence indicates that infusions are independent of aqueous synthesis rate, and that vasopressin, acting on a V1 receptor subtype reached from the anterior chamber, exerts a vascular effect.
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PMID:Interaction between head-down tilt and anterior chamber infusions on intraocular pressure of anesthetized rats. 898 44

Continuous intracameral infusions of a balanced salt solution (0.175 microliter min-1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 microliter-1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049-0.35 microliter min-1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 microliter min-1) and a larger periodic component (0.25 microliter min-1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 microliter min-1. As shown previously for 0.175 microliter min-1 constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops.
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PMID:Mechanisms for vasopressin effects on intraocular pressure in anesthetized rats. 946 85

The activity on intraocular pressure (IOP) of SR121463, a selective non-peptide arginin-vasopressin (AVP) V2 receptor antagonist, was investigated in a rabbit model of ocular hypertension. We first demonstrated that, in vitro, SR121463 displayed high competitive affinity for rabbit vasopressin V2 receptors (Ki = 2.1 +/- 1.2 nM). In vivo, SR121463 was instilled once (at concentrations ranging from 0.1 to 3%), or for 10 days (20 instillations) at 1% concentration, in the eye of ocular hypertensive rabbits (intraocular injection of 0.14 mg alpha-chymotrypsin). SR121463 also was instilled at 1% in the normotensive eye or intravenously injected (100 microg/kg) to ocular hypertensive rabbits. SR121463 was compared to timolol 0.5% or to clonidine 0.25%. Additionally, local and systemic safety aspects were examined. Results showed that SR121463 was locally well-tolerated and had no anesthetic effect. A significant decrease in IOP of the hypertensive eye was observed for concentrations of SR121463 > or =1%. This decrease was comparable to that obtained with reference compounds. A similar activity was found after intravenous administration. No tachyphylaxis was observed after 10 days, and no contralateral or systemic effect was noted. Also, when applied on the normotensive eye or when intravenously injected, SR121463 had no effect on the normotensive eye. These results on IOP and the good local and systemic safety profile, suggest that a potent vasopressin V2 receptor antagonist, SR121463, could be of value for the treatment of glaucoma, through a mechanism of action that remains to be elucidated.
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PMID:Effect of SR121463, a selective non-peptide vasopressin V2 receptor antagonist, in a rabbit model of ocular hypertension. 1087 18

SR121463 is a selective, orally active, non-peptide antagonist of vasopressin (AVP) V(2) receptors with powerful aquaretic properties in various animal species and humans. SR121463 belongs to a new class of drugs, called aquaretics, which are capable of inducing free-water excretion without affecting electrolyte balance. SR121463 displays high affinity for animal and human V(2) receptors and exhibits a remarkably selective V(2) receptor profile. SR121463 and [(3)H]SR121463 are used, therefore, as selective probes for characterization and labeling of V(2) receptors. In various functional studies in vitro, SR121463 behaves as a potent antagonist. It inhibits AVP-stimulated human renal adenylyl cyclase and dDAVP (1-desamino, 8-D arginine-vasopressin)-induced relaxation of rat aorta. SR121463 also behaves as an inverse agonist in cells expressing a constitutively activated human V(2) receptor mutant. In vitro, SR121463 rescued misfolded V(2) AVP receptor mutants by increasing cell surface expression and restoring V(2) function. In normally hydrated conscious rats, dogs and monkeys, SR121463, by either i.v. or p.o. administration, induced a dose-dependent aquaresis with no major changes in urinary Na+ and K+ excretion (unlike classical diuretics). In cirrhotic rats with ascites and impaired renal function, a 10-day treatment with SR121463 totally corrected hyponatremia and restored normal urine excretion. In a model of diabetic nephropathy in rats, SR121463 strongly reduced albumin excretion. SR121463 was also effective at extrarenal V(2) (or V(2)-like) receptors involved in vascular relaxation or clotting factor release in vitro and in vivo. In the rabbit model of ocular hypertension, SR121463 by either single or repeated instillation, decreased intraocular pressure. After acute and chronic administration to rats, dogs or healthy human volunteers, SR121463 was well absorbed and well tolerated. In all species studied the drug produced pronounced aquaresis without any agonist effect. Thus, SR121463 is a potent, orally active and selective antagonist at V(2) receptors with powerful aquaretic properties. It is a useful tool for further exploration of function of renal or extrarenal V(2) receptors. Pure V(2) receptor antagonists are likely to be therapeutically useful in several water-retaining diseases such as hyponatremia, Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH), congestive heart failure, liver cirrhosis, and other disorders possibly mediated by V(2) receptors (e.g., glaucoma).
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PMID:An overview of SR121463, a selective non-peptide vasopressin V(2) receptor antagonist. 1160 38

The aim of the present paper is to study the relation between vasopressin antagonism and the regulation of intraocular pressure (IOP). From the studies on the effect of several vasopressin receptor antagonists, VP-343, OPC-21268, YM087, OPC-31260 and SR121463, on normal IOP and the effect of VP-343 on pupil diameter in rabbit, it was shown that some vasopressin antagonists decreased normal IOP and VP-343 had no influence on pupil diameter. A vasopressin receptor mapping study in normal cynomolgus monkey eye revealed a high density binding site for a [H3]vasopressin V1 antagonist in the region of iris. These findings suggest that a vasopressin antagonist should decrease normal IOP without miosis and that vasopressin V1 receptors are present in iris.
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PMID:The effects of several vasopressin receptor antagonists on normal intraocular pressure and the intraocular distribution of vasopressin receptor subtypes. 1185 77


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