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)

1. The effects of two doses of clonidine (100 and 500 micrograms/kg sc) were compared on several types of experimentally induced diuresis (total value during 4 hours): alcohol or water loaded rats and Brattleboro rats (i.e. animals with congenital lack of vasopressin). 2. The two doses of clonidine alone increased the values of urine flow (fig. 1 and 3). 3. Clonidine, at a low dosage (100 micrograms/kg sc), potentiated the increase in urine flow induced by water overloading but remained ineffective in alcohol--loaded rats (fig. 1). 4. Clonidine, at a higher dosage (500 micrograms/kg sc) reduced alcohol--or water--induced diuresis (fig. 3). 5. In Brattleboro rats, clonidine decreased urine flow (100 micrograms/kg sc) or was without effect (500 micrograms/kg sc) (fig. 2). 6. These results suggest that relatively high doses of clonidine may be useful in treatment of alcohol with drawal in man: the drug could act as a sympatholytic and sedative central agent but could also decrease alcohol--induced diuresis by inhibition of vasopressin release.
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PMID:[Effect of clonidine on polyuria induced by alcohol, water or the lack of vasopressin in the rat]. 715 68

1. The effects of clonidine on water balance were compared in normal (N.) and diabetes insipidus (Brattleboro D.I.) conscious rats. Animals were housed in individual cages and feed food and water ad libitum. The dose of clonidine was 100 microgram . kg-1 by subcutaneous route during consecutive 9 days. A control period of 12 days without drug treatment (only saline as a sham injection) separated the different period treatments. Under these experimental conditions the values of diuresis, water and food intakes, blood pressure were measured every morning before clonidine-treatment. 2. In normal rats, clonidine induced a diuretic and dipsogenic action (fig. 1). In contrast, the drug elicited an antidipsogenic and antidiuretic response in D.I. rats (fig 2). 3. In another series of experiments, the short term responses to clonidine treatment were studied in the two groups of animals. During the two first hours of treatment, clonidine elicited a rapid and marked reduction in water intake in the two groups of animals (table I). In normal rats, the drug also elicited an increase in urine flow. In contrast, in D.I. (Brattleboro) rats, an antidiuretic effect was observed during the first 30 minutes after clonidine- injection but not during the following 30 minutes periods (fig 3). 4. Clonidine increased both the natriuretic and kaliuretic excretion in normal rats, but failed to modify these values in D.I. rats (fig 4). 5. Clonidine decreased blood pressure in the two groups of animals (table II) but failed to modify the values of food intake (table III). 6. These results suggest that clonidine-induced diuresis is related to inhibition of vasopressin (ADH) secretion. Since the early observation of water balance revealed a clonidine antidipsogenic-induced effect in the two groups of animals, it is suggested that vasopressin was not involved in the clonidine induced water intake and that the daily antidiuretic response in Brattleboro (D.I.) rats was only related to the antidipsogenic property of clonidine.
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PMID:[Effects of clonidine on diuresis and water intake in normal and Brattleboro rats. (author's transl)]. 728 24

Acute renal failure was produced in vasopression-pretreated rabbits by clamping the left renal pedicle for one hour and removing the opposite kidney. Treatment with clonidine, as antihypertensive drug that blunts the kidney's response to vasopressin, resulted in significantly higher creatinine clearance and urine flow rate in the first 6 hours after unclamping. Clonidine (30 microgram/kg given intravenously 30 minutes before unclamping) also significantly lessened the number of hyaline casts in outer medullary tubules and inner medullary loops of Henle 6 hours after unclamping and reduced the number of abnormal tubular contours in microadiograms produced by infusing barium sulfate into the renal artery at sufficient pressure to rupture glomerular capillaries, causing an escape of contrast material into the tubules. The spaces consistently observed between the ends of barium columns and hyaline casts in microdissection studies and the great lengths of the hyaline casts suggest that hyaline casts obstruct the flow of tubular fluid. Clonidine treatment resulted in fewer, shorter, and thinner hyaline casts. These results indicate that tubular obstruction by hyaline casts plays an important role in early postischemic acute renal failure, and that clonidine's beneficial effect is due in part to a reduction in cast formation.
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PMID:The effect of clonidine on tubular obstruction in postischemic acute renal failure in the rabbit demonstrated by microradiography and microdissection. 735 Aug 13

Clonidine, an alpha adrenergic agonist which causes a diuresis in experimental animals, was studied in unanesthetized, conscious Brattleboro rats heterozygous or homozygous for hereditary hypothalamic diabetes insipidus to determine if the diuresis was due to alpha adrenergic inhibition of antidiuretic hormone (ADH) release or to another mechanism of action. Heterozygous rats given clonidine s.c. in doses of 50 to 300 mu/kg b.w. exhibited a prompt dose-related diuresis. The diuresis was transient and could not be maintained beyond 4 hr even when clonidine was administered continuously by s.c. osmotic minipump. In response to clonidine-induced diuresis, plasma osmolality increased acutely from 300 +/- 1 to 310 +/- 1 mOsM/kg by 60 min after injection. Base-line plasma ADH was 5.1 +/- 0.9 mu/ml, remained unchanged at 15 min after clonidine injection but increased to 21.6 +/- 7.2 muU/ml by 60 min and was accompanied by an increase in urinary ADH excretion from 19.6 +/- 3.7 to 48.6 +/- 5.3 muU/hr. In parallel with the drug-induced diuresis, there was an increase in urinary excretion of creatinine, sodium and total solute. The alpha blocking agent phenoxybenzamine did not prevent the diuresis after clonidine injection. Clonidine antagonized the antidiuresis after clonidine injection. Clonidine antagonized the antidiuretic action of ADH administered to rats homozygous for diabetes insipidus. Thus, clonidine-induced diuresis does not appear to be due to alpha adrenergic inhibition of ADH release but rather to direct renal effects.
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PMID:Clonidine-induced diuresis in the rat: evidence for a renal site of action. 740 Sep 63

Clonidine, an antihypertensive drug that inhibits renin release and causes a water diuresis in normal animals, was tested for its ability to reduce the severity of post-ischemic acute renal failure produced in rabbits by clamping the left renal pedicle for 1 hour and removing the opposite kidney. Clonidine significantly lessened renal failure when given during, or 1 hours after, the ischemic insult in dehydrated rabbits. It was also effective when given during the ischemic insult in vasopressin-treated water-drinking rabbits but not in control water-drinking rabbits. In vasopressin-treated rabbits, clonidine lessened renal failure observed 2 days after the ischemic insult despite the fact that in the immediate postischemic period it lowered total renal blood flow, produced hypotension, and did not bring about lower plasma renin levels. Clonidine treatment resulted in less outer medullary microvascular damage (demonstrated by colloidal carbon staining), higher outer medullary blood flow 1 to 2 hours after unclamping, fewer casts, and higher creatinine clearance and free water clearance/creatinine clearance 4 to 6 hours after unclamping compared with controls. The effect of clonidine was unrelated to plasma renin activity. Clonidine did not alter plasma vasopressin concentration. Demeclocycline and lithium, two agents that blunt renal responsiveness to vasopressin, had a beneficial effect in dehydrated animals similar to that of clonidine, but the angiotensin II antagonist saralasin and the angiotensin converting enzyme inhibitor SQ20881 did not. Normal rabbits given a large dose of vasopressin in oil plus clonidine had significantly greater urine output and free water clearance and lower urine osmolality than did rabbits given vasopressin in oil alone. These results suggest that clonidine may be beneficial because it prevents ischemic microvascular injury in the renal outer medulla, an effect that may decrease tubular obstruction by lessening desquamation of damaged tubular cells or cell constituents into the tubular lumen. Clonidine may also decrease formation of obstructive hyaline casts in collecting ducts by blunting the kidney's response to vasopressin and increasing tubular fluid flow rate.
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PMID:Clonidine after renal ischemia to lessen acute renal failure and microvascular damage. 746 46

The effects of clonidine, vasopressin or a combination of both substances on splanchnic and systemic haemodynamics were measured in conscious rats with portal vein stenosis. Clonidine alone significantly decreased portal pressure, portal tributary blood flow and cardiac index, but did not change arterial pressure. Vasopressin alone significantly increased arterial pressure and significantly decreased portal pressure, portal tributary blood flow and cardiac index. Changes in portal tributary blood flow, arterial pressure and cardiac index were significantly higher with vasopressin than with clonidine alone. Vasopressin infusion in rats pretreated with clonidine significantly increased arterial pressure and significantly decreased portal pressure, portal tributary blood flow and cardiac index. Changes in arterial and portal pressures and portal tributary blood flow were significantly higher with combined therapy than with clonidine alone. Changes in arterial and portal pressures and portal tributary blood flow did not differ between combined therapy and vasopressin alone. Changes in cardiac index were significantly higher with combined therapy than with clonidine or vasopressin alone. Hepatic artery blood flow was not affected by either clonidine or vasopressin but significantly declined with combined therapy. In conclusion, this study suggests that a combination of vasopressin and clonidine accentuates the portal hypotensive action of clonidine but not the action of vasopressin. Moreover, this study suggests that a combination of vasopressin and clonidine may have deleterious effects on systemic and hepatic artery vascular beds.
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PMID:Effects of vasopressin on haemodynamics in portal hypertensive rats receiving clonidine. 817 29

The utility of clonidine for hypertensive patients presenting for major vascular procedures remains debatable. Twenty-one hypertensive patients presenting for aortic surgery were given clonidine (n = 11) or placebo (n = 10) in a double-blind, randomized manner. Clonidine was administered 6 micrograms/kg per os 120 min before induction of anesthesia and 3 micrograms/kg intravenously (i.v.) over 60 min from aortic declamping to skin closure. Anesthesia was induced with alfentanil 20 micrograms/kg, midazolam, and atracurium and maintained with nitrous oxide 70%, an alfentanil infusion (0.25 microgram.kg-1. min-1), and isoflurane. Anesthetic requirements, circulatory variables, interventions, and isoproterenol dose-response curves (pre- and postoperatively) were determined. Plasma concentrations of clonidine, alfentanil, and vasoactive hormones were measured. When the clonidine group was compared with the placebo group, (a) isoflurane, alfentanil, and midazolam requirements were reduced by 38%, 42%, and 41%, respectively (P = 0.04, 0.03, 0.0002, respectively); (b) supplemental circulatory and anesthetic adjustments were reduced by 51% (P = 0.0006); (c) interventions with vasopressors were not significantly increased (placebo: two; clonidine: five); (d) systolic and mean arterial pressures and heart rate were reduced; (e) increases in norepinephrine, epinephrine, and plasma renin activity were suppressed, whereas vasopressin surge was attenuated; and (f) chronotropic response to isoproterenol was unaffected. Clonidine was effective in reducing anesthetic requirements and in improving circulatory stability in hypertensive patients presenting for major vascular procedures.
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PMID:Clonidine for major vascular surgery in hypertensive patients: a double-blind, controlled, randomized study. 883 4

Rat liver plasma membranes reconstituted with bovine brain phospholipase C beta 1 (PLC- beta 1) exhibit a dual regulation of PLC- beta 1 activity by G-proteins. Guanosine 5'-[gamma-thio]triphosphate (GTP[S]; 0.1 nM) produced a 20-25% inhibition of PLC- beta 1 activity within 7 min of incubation. The addition of vasopressin resulted in near-basal levels of activity in the presence of 0.1 nM GTP[S]. Clonidine had little effect on the net inhibition due to GTP[S]. A similar antagonism between carbachol and GTP[S] occurred in cerebral cortical membranes containing endogenous PLC- beta 1 activity. alpha 0/i-GDP (a mixture of GDP-liganded G0 alpha and Gi alpha) attenuated the GTP[S]-dependent inhibition of PLC- beta 1 whereas alpha 0/i-GTP[S] had no effect, suggesting an involvement of G-protein beta gamma subunits in the inhibition of PLC- beta 1. Low concentrations of beta gamma subunits inhibited PLC- beta 1 activity. Inhibition was followed by reversal to basal activity and onset of stimulation as the beta gamma concentration was increased. Inhibition by beta gamma was dependent on the presence of membranes. These results indicate that G-protein beta gamma subunits constitute a mechanism by which G-protein mediate a rapid and transient inhibition of PLC- beta 1.
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PMID:G-protein inhibition of phospholipase C-beta 1 in membranes: role of G-protein beta gamma subunits. 887 Jun 65

The effects of a new transdermal delivery system for clonidine (M-5041T) on hypotensive effect, urine volume, plasma renin activity (PRA) and antidiuretic hormone (ADH) in spontaneously hypertensive rats (SHRs) were compared to the effects of the continuous infusion of clonidine. Both M-5041T (1.5 and 4.5 mg/kg) and the continuous infusion of clonidine (250 micrograms/kg/24 h) elicited hypotensive effects persisting for 12 hours or more. These effects were based on consistent plasma concentrations of clonidine. These two treatments produced diuresis followed by antidiuresis, which was remarkably observed by continuous infusion of clonidine. Single subcutaneous injection of clonidine (50 micrograms/kg) produced diuresis accompanied by increases in electrolytes corresponding to plasma levels of clonidine. M-5041T at 1.5 mg/kg did not affect PRA until 12 h, and produced an increase in PRA at 24 h. M-5041T at 4.5 mg/kg and the continuous infusion of clonidine resulted in a decrease in PRA at 2 and 1 h followed by an increase at 12 and 24 h, respectively. M-5041T at 1.5 mg/kg did not affect plasma levels of ADH. Plasma ADH did increase at 2 and 4 h accompanied by diuresis following M-5041T at 4.5 mg/kg or the continuous infusion of clonidine, respectively. Clonidine-induced diuresis was not at least due to the inhibition of ADH release. The decrease in urine volume observed by continuous infusion of clonidine may be due to decrease in renal blood flow based on stimulation of peripheral adorenoceptors of clonidine. These findings suggest that the increases in ADH and PRA are due to the compensatory effects related to both diuresis and the long-lasting hypotensive effect induced by high plasma concentrations of clonidine. Thus, it can be expected that M-5041T at 1.5 mg/kg showing the minimum effective plasma concentration of clonidine will not result in tolerance to the hypotensive effect of clonidine associated with the retention of sodium in SHRs.
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PMID:Preclinical assessment of a new transdermal delivery system for clonidine (M-5041T). 890 May

The alpha2-adrenergic agonist clonidine and the neuropeptide oxytocin, inhibit sodium intake when injected intracerebroventricularly (i.c.v.). The present work investigates whether (1) vasopressin also inhibits sodium intake when injected i.c.v., and (2) the effect of oxytocin and of vasopressin on sodium intake is affected by i.c.v. injection of idazoxan, an alpha2-adrenergic antagonist. Clonidine (30 nmol), oxytocin (40, 80 nmol) and vasopressin (40, 80 nmol) were injected i.c.v. 20 min prior to a 1.5% NaCl appetite test, in rats depleted of sodium for 24 h by a combination of a single s.c. injection of furosemide (10 mg/rat) and removal of ambient sodium. Every dose of clonidine, oxytocin and vasopressin inhibited the 1.5% NaCl intake. Seizures were observed with the higher dose of vasopressin, but not with either dose of oxytocin. The effect of i.c.v. injection of clonidine (30 nmol), oxytocin (80 nmol) or vasopressin (40 nmol) was partially inhibited by prior i.c.v. injection of idazoxan (160, 320 nmol). The results suggest that the inhibition of 1.5% NaCl intake induced by i.c.v. injection of neuropeptides in sodium-depleted rats depends, in part, on the activation of central alpha2-adrenoceptors.
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PMID:Idazoxan and the effect of intracerebroventricular oxytocin or vasopressin on sodium intake of sodium-depleted rats. 922 97


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