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 rate of water uptake across the skin was studied in the live toad, Bufo melanostictus. When toads were kept in distilled water at 29 degrees C the uptake of water amounted to 16.9 +/- 1.3 mul./cm(2)/hr; when bathed in sucrose or urea solutions, the water uptake diminished with increasing osmotic pressure. There was no water uptake observed when toads were kept in 200 m-osmolar sucrose or urea.2. Intramuscular injections of vasopressin increased the rate of water uptake from distilled water. There was a good relation between doses and responses over various time intervals. A dose of 4 m-u. vasopressin/g body wt. doubled the rate of water uptake over a period of 1 hr. The same dose of vasopressin doubled the rate of water uptake when the toads were kept in solutions of sucrose or urea of different osmolarity.3. The rate of water uptake when the toads were bathed in sodium chloride solutions was consistently 8 mul./cm(2)/hr greater than when bathed in sucrose or urea solutions of equal osmolarity. There was no water uptake when the sodium chloride solution was 285 m-osmolar.4. Vasopressin (4 m-u./g) injected intramuscularly doubled the rate of water uptake from sodium chloride solutions of different osmolarity.5. With solutions of potassium chloride, sodium nitrate, and potassium nitrate, in concentrations up to 150 m-osmoles/l., the rate of water uptake was found to be the same as with solutions of sodium chloride of the same osmolarity. Similarly, it was doubled by injection of vasopressin (4m-u./g).6. The effect of temperature on the rate of water uptake before and after injection of vasopressin was investigated in toads kept in distilled water, sucrose, or sodium chloride solutions. For temperatures between 20 and 37 degrees C, vasopressin (4 m-u./g) reduced the activation energy involved in the process of water uptake by 4000 cal.7. The results agree with the view that water uptake follows a diffusion process which is facilitated by vasopressin, possibly as a result of increasing the size or number of available pores.
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PMID:Water uptake by Bufo melanostictus, as affected by osmotic gradients, vasopressin and temperature. 604 6

Intracerebroventricular injections of selective opioid agonists were used to investigate the role of opiate receptor subtypes in cardiovascular function in awake rats. The mu-agonist (D-Ala2,MePhe4,Gly5-ol)enkephalin (1 nmol) caused a prolonged increase in blood pressure and an initial decrease followed by a delayed increase in heart rate. These effects were antagonized by the selective mu-antagonist beta-funaltrexamine. A selective delta-agonist (dimeric tetrapeptide enkephalin) was devoid of cardiovascular effects at 10 nmol, whereas a benzomorphan kappa-agonist MRZ caused a pressor response which was not antagonized by beta-funaltrexamine. The mechanisms by which opioids elicit cardiovascular effects were analyzed in detail by using microinjections into the anterior hypothalamic area. Low doses of enkephalin produced increases in heart rate and blood pressure. Associated elevations of plasma norepinephrine and epinephrine, but not vasopressin, suggested a stimulation of sympatho-adrenomedullary pathways. Higher doses caused increases in blood pressure but decreases in heart rate. Peripheral vagal blockade with atropine methyl nitrate caused a large sudden rise in heart rate, indicating that an increased vagal outflow counteracted the sympathetic activation. Adrenal demedullated rats displayed no tachycardia after anterior hypothalamic injection of low doses of enkephalin, whereas high dose caused pronounced bradycardia. Additional treatment of demedullated rats with the sympathetic blocker bretylium led to severe hypotension in addition to bradycardia. These data provide evidence that mu-opiate receptors primarily mediate cardiovascular effects of opiates in awake rats. At low doses, a sympathetic adrenomedullary activation occurs, whereas higher doses additionally activate parasympathetic efferents, both possibly from anterior hypothalamic sites.
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PMID:Mu-receptors mediate opioid cardiovascular effects at anterior hypothalamic sites through sympatho-adrenomedullary and parasympathetic pathways. 630 71

Nitric oxide derived from vascular endothelium is a potent vasodilator that plays a key role in the homeostasis of blood pressure. Because cirrhotic patients tend to have low arterial pressure, we measured in 51 patients and 10 control subjects serum nitrite and nitrate levels as an index of in vivo nitric oxide generation. We also measured plasma endotoxin, a substance frequently increased in cirrhotic patients and known to induce nitric oxide synthesis. Cirrhotic patients showed significant increases in serum nitrite/nitrate and plasma endotoxin compared with controls. Values were particularly increased in patients with decompensated cirrhosis, as manifested by ascites with or without functional kidney failure. High serum nitrite/nitrate levels were associated with high plasma renin activity, high aldosterone and antidiuretic hormone levels and low urinary excretion of sodium. In addition, serum nitrite/nitrate levels significantly correlated with endotoxemia. Oral administration of colistin to 15 cirrhotic patients reduced significantly plasma endotoxin levels (p < 0.01) and serum nitrite/nitrate levels (p < 0.05). Because endotoxin enhances the expression of inducible nitric oxide synthase, our results suggest that circulating endotoxin in cirrhosis is responsible for excessive synthesis and release of nitric oxide by the vasculature. These findings might explain the hemodynamic dysfunction seen in cirrhotic patients.
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PMID:Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia. 822 20

A series of 5-deoxy-5-(4-substituted piperazin-1-yl)-1,4: 3,6-dianhydro-L-iditol 2-nitrates was prepared and evaluated for oral anti-ischemic activities. Inhibition of lysine-vasopressin-induced T-wave elevation in the electrocardiogram (ECG) of rats (angina pectoris model) served as a primary assay. Optimum activity was observed for the compounds with the aryl-heteroatom (O,S, or N)-propyl group. Among them, the phenylthiopropyl-substituted compound 13 exhibited the most potent activity. Furthermore, intraduodenal administration (i.d.) of 13 tended to decrease left ventricular end-diastolic pressure (LVEDP) in a propranolol-induced heart failure model (dogs) and showed a potent protective effect against reperfusion arrhythmia in rats. Thus, 13 (KF 14124) is under further study as an orally active nitrate.
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PMID:1,4:3,6-Dianhydrohexitol nitrate derivatives. I. Synthesis and antianginal activity of alkylpiperazine derivatives. 837 Jan 9

A series of 5-(4-aryl- or 4-arylcarbonylpiperazin-1-yl)-5-deoxy-1,4: 3,6-dianhydro-L-iditol 2-nitrates was prepared in order to obtain orally active, nitrate-type vasodilators with reduced side effects. Our drug design was based on a small reduction in the lipophilicity compared to that of 5-deoxy-5-[4-(3-phenylthiopropyl)piperazin-1-yl]-1,4: 3,6-dianhydro-L-iditol 2-nitrate (1, KF14124). Compounds 4h (aryl = benzimidazol-2-yl), 4i (arylcarbonyl = nicotinoyl), and 4w (arylcarbonyl = 3-furoyl) showed potent anti-ischemic activity in a lysine-vasopressin-induced angina pectoris model (rats), and their structure-activity relationships are discussed. Compound 4i exhibited potent vasodilation of the coronary artery in anesthetized dogs and also exhibited potent preload reduction in a heart failure model (dogs) as compared with isosorbide dinitrate (2), nicorandil (3), and KF14124 (1). Furthermore, 4i showed much weaker acute lethal toxicity and less central nervous system depression than 1 in mice. Thus, 4i (KW-3196) is under development as a vasodilator and a drug for treating angina pectoris.
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PMID:1,4:3,6-Dianhydrohexitol nitrate derivatives. II. Synthesis and antianginal activity of aryl- or arylcarbonylpiperazine derivatives. 837 Jan 10

Bleeding may become a major impediment to accurate and safe dissection by laparoscopy. The traditional maneuvers of pressure, dumping, irrigation, and aspiration frequently applied during open procedures to maintain a clear field of dissection are cumbersome through laparoscopy. Several pharmacologic agents have been used topically or by local injection to stop bleeding or to prevent excessive blood loss during surgical procedures. They include calcium alginate, aluminum salts, silver nitrate, formalin, and coagulating agents like thrombin and collagens, all of which leave a layer of damaged tissue or foreign material on the surface. Epinephrine and vasopressin have been employed mostly by local injections. We report the use of topical epinephrine applied before and during the dissection of the cystic duct and artery area in the course of laparoscopic cholecystectomy. A 3/8-inch gauze sponge, impregnated with a 1:10,000 epinephrine solution, was used to blanch the tissues and to bluntly dissect the cystic duct and artery. It was also used to control minor bleeding in the gallbladder fossa. The prophylactic bleeding control with topical epinephrine proved to be an easy and safe maneuver, and greatly facilitated the dissection of the most critical areas during laparoscopic cholecystectomy. This technique may be applicable to laparoscopic dissection for other procedures.
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PMID:Pharmacologic hemostasis in laparoscopy: topical epinephrine facilitates cholecystectomy. 848 94

The anti-ischemic effects of organic nitrates are rapidly attenuated due to the development of nitrate tolerance. The mechanisms underlying this phenomenon likely involve several independent factors. As a vasodilator, nitroglycerin activates compensatory neurohumoral mechanisms such as the renin-angiotensin system and increases catecholamine and vasopressin levels, all of which may attenuate its vasodilator potency. Tolerance may be also due to the inability of the vessel to dilate after prolonged treatment with the nitrate. More recent experimental studies have challenged traditional tolerance concepts by demonstrating that tolerance is not associated with sulfhydryl group depletion, reduced nitroglycerin biotransformation, or desensitization of the target enzyme guanylyl-cyclase. Experimental and clinical observations suggest that tolerance may be the consequence of intrinsic abnormalities of the vasculature, including enhanced endothelial production of oxygen-derived free radicals secondary to an activation of NAD(P)H-dependent oxidases and an activation of PKC. Superoxide degrades nitric oxide derived from nitroglycerin (NTG) while C activation causes enhanced sensitivity of the vasculature to circulating neurohormones such as catecholamines, angiotensin II, and serotonin, all of which may compromise the vasodilator potency of NTG. Interestingly, these vascular consequences of in vivo NTG treatment such as superoxide production and PKC activation can be mimicked in vitro by incubating cultured endothelial and smooth muscle cells with angiotensin II. Furthermore, nitrate tolerance and rebound following sudden cessation of prolonged NTG therapy can be prevented by concomitant treatment with high-dose angiotensin-converting enzyme inhibition, angiotensin type 1 receptor blockade, or antioxidants such as hydralazine. Thus one can conclude that neurohumoral counterregulatory mechanisms such as increased circulating levels of angiotensin II may be at least in part responsible for tolerance mechanisms at the cellular level.
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PMID:Evidence for a role of oxygen-derived free radicals and protein kinase C in nitrate tolerance. 942 22

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.
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PMID:Antipyretic role of nitric oxide during endotoxin-induced fever in rabbits. 950 19

The effects of the acute administration of arterial vasoconstrictors on renal plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrhotic patients with ascites with or without hepatorenal syndrome (HRS) are still controversial. As a consequence, vasoconstrictors are not actually used in the treatment of renal sodium retention or HRS in these patients, regardless of the several lines of evidence suggesting that these renal functional abnormalities are related to a marked arterial vasodilation. The lack of an orally available effective arterial vasoconstrictor probably represents a further reason for this omission. Consequently, the present study was made to evaluate the acute effects of the oral administration of midodrine, an orally available -mimetic drug, on systemic and renal hemodynamics and on UNaV in cirrhotic patients with ascites. Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic vascular resistance (SVR), left forearm blood flow (LFBF), left leg blood flow (LLBF), RPF, glomerular filtration rate (GFR), UNaV, plasma renin activity (PRA), plasma concentration of antidiuretic hormone (ADH), and the serum levels of nitrite and nitrate (NOx) were evaluated in 25 cirrhotic patients with ascites (17 without HRS and 8 with type 2 HRS) before and during the 6 hours following the oral administration of 15 mg of midodrine. During the first 3 hours after the drug administration, a significant increase in MAP (89.6 +/- 1.7 vs. 81.80 +/- 1.3 mm Hg; P < .0001) and SVR (1, 313.9 +/- 44.4 vs. 1,121.2 +/- 60.1 dyn . sec . cm-5; P < .0001) accompanied by a decrease in HR (69 +/- 2 vs. 77 +/- 3 bpm; P < .005) and CI (2,932.7 +/- 131.4 vs. 3,152.5 +/- 131.4 mL . min-1 . m2 BSA; P < .0025) was observed in patients without HRS. No change was observed in LFBF and LLBF. The improvement in systemic hemodynamics, which was also maintained during the the 3- to 6-hour period after midodrine administration, was accompanied by a significant increase in RPF (541.5 +/- 43.1 vs. 385.7 +/- 39.9 mL . min-1; P < .005), GFR (93.1 +/- 6.5 vs. 77.0 +/- 6.7 mL . min-1; P < .025), and UNaV (92.7 +/- 16.4 vs. 72.2 +/- 10.7 microEq . min-1; P < .025). In addition, a decrease in PRA (5.33 +/- 1.47 vs. 7.74 +/- 2.17 ng . mL-1 . h; P < .05), ADH (1.4 +/- 0.2 vs. 1.7 +/- 0.2 pg . mL-1; P < .05), and NOx (33.4 +/- 5.0 vs. 49.3 +/- 7.3 micromol-1; P < .05) was found. In patients with HRS, the effects of the drug on the systemic hemodynamics was smaller and shorter. Accordingly, regardless of a significant decrease in PRA (15.87 +/- 3.70 vs. 20.70 +/- 4.82 ng . mL-1 . h; P < .0025) in patients with HRS, no significant improvement was observed in RPF, GFR, or UNaV. In conclusion, the acute oral administration of midodrine is associated with a significant improvement in systemic hemodynamics in nonazotemic cirrhotic patients with ascites. As a result, renal perfusion and UNaV also improve in these patients. By contrast, midodrine only slightly improves systemic hemodynamics in patients with type 2 HRS, with no effect on renal hemodynamics and renal function.
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PMID:Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites. 975 29

The cardiovascular profile of the angiotensin AT1 receptor antagonist, GR138950, and the influence of potential compensatory homeostatic mechanisms on this profile, were investigated in renal artery ligated hypertensive (RALH) rats. GR138950 caused a marked reduction in blood pressure associated with immediate tachycardia in conscious RALH rats. The antihypertensive action of GR138950 appeared biphasic; an immediate fall in blood pressure, which plateaued within 1 h, and which was followed by a further slow decline that reached maximum between 5-7 h after administration. The tachycardia caused by GR138950 was attenuated by atenolol and was abolished by combined pretreatment with atenolol and atropine methyl nitrate. However, the antihypertensive profile of GR138950 was unchanged by these pretreatments. The resting blood pressure and the antihypertensive effect of GR138950, in RALH rats, were unaffected by the vasopressin V1 receptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylene propionyl(1)-O-Me-Tyr2,Arg8]-vasopressin. Thus, vasopressinergic mechanisms are not involved in either maintaining blood pressure in RALH rats, or in compensating for the fall in blood pressure caused by GR138950. In anaesthetized RALH rats, GR138950 caused a marked fall in blood pressure that was accompanied by an increase in heart rate along with sustained increases in renal and splanchnic sympathetic nerve activity. In summary, the biphasic fall in blood pressure evoked by GR138950 in RALH rats can not be explained on the basis of changes in autonomic control of the heart, alteration of vasopressin-mediated vasoconstrictor mechanisms or overall suppression of central sympathetic outflow. Rather, increased vasoconstrictor tone might serve to oppose the initial fall in blood pressure.
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PMID:The antihypertensive profile of the angiotensin AT1 receptor antagonist, GR138950, and the influence of potential homeostatic compensatory mechanisms in renal hypertensive rats. 986 52


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