UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of torasemide (0.1 and 1 mg kg-1, i.v.) and furosemide (3 mg kg-1) on renal haemodynamics and excretory responses in the presence of angiotensin II and endothelin-1 was examined in anaesthetized dogs. Angiotensin II or endothelin-1 was continuously infused into the renal artery throughout the experiment and a bolus of torasemide or furosemide was injected into the bracheal vein. Continuous intrarenal arterial (i.r.a.) infusion of angiotensin II, at a dose of 5 ng kg-1 min-1, increased renal vascular resistance (RVR) and decreased renal blood flow (RBF) and glomerular filtration rate (GFR), but had no effect on systemic mean arterial pressure (MAP). Urinary excretion of sodium (UNaV) and urine flow (UF) were significantly decreased during angiotensin II infusion. Intravenous injections of torasemide in the presence of angiotensin II caused a dose-dependent increase in UF, UNaV and urinary excretion of potassium (UKV), while a decrease in RVR was accompanied by an increase in RBF. UKV was greater in the furosemide group than in the torasemide group, despite both groups having the same degree of aquaresis and natriuresis. Continuous i.r.a. infusion of endothelin-1, 1.5 ng kg-1 min-1, produced effects similar to those of angiotensin II on renal haemodynamics; however, the onset of action was extremely slow compared with the effects produced by angiotensin II. Endothelin-1 caused a significant decrease in UF, UNaV and UKV only at a later period, despite a relatively early depression of renal haemodynamics. Torasemide and furosemide also produced a sufficient diuretic action in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diuretic action of the novel loop diuretic torasemide in the presence of angiotensin II or endothelin-1 in anaesthetized dogs. 135 Jun 26

1. The interactions between angiotensin II (AII), two non-peptide antagonists DuP 753 and IMI, and eight peptide analogues of AII were investigated on the rabbit isolated aorta assay. DuP 753 and IMI behaved as simple competitive antagonists (pKB values 8.4 and 6.8, respectively). To different degrees, all the AII-peptide analogue interactions failed to meet the basic criteria for simple competition. In addition to rightward shift, the most significant feature was a concentration-dependent saturable depression of the upper asymptote of the AII concentration-effect curves. 2. 'Washout' and combined dose-ratio analysis experiments, in which DuP 753 was used as a reference antagonist, indicated that the profile of peptide antagonism was solely due to a reversible and syntopic action at the AII receptor. 3. By use of an operational model of agonism (Black & Leff, 1983) as a starting point, it was possible to account for the data with a new model which describes reversible receptor occupancy and occupied receptor-determined, saturable reduction in the efficacy of AII. Model-fitting gave estimates of pKB values for the peptide analogues and agonist affinity and efficacy parameters for AII. 4. The model was successfully tested by applying it to qualitatively similar results obtained in a cross-tissue analysis on guinea-pig aorta, ileum and stomach. 5. A 'molecular' interpretation of the efficacy changes, based on the concepts of receptor internalisation and expression, is offered.
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PMID:Evidence that the apparent complexity of receptor antagonism by angiotensin II analogues is due to a reversible and syntopic action. 139 59

1. The M-like current IK(M,ng) in differentiated NG108-15 mouse neuroblastoma x rat glioma hybrid cells has been studied using tight-seal, whole-cell patch-clamp recording. 2. When calculated from steady-state current-voltage curves, the conductance underlying IK(M,ng) showed a Boltzmann dependence on voltage with half-activation voltage Vo = -44 mV (in 3 mM [K+]) and slope factor (a) = 8.1 mV/e-fold increase in conductance. In 12 mM [K+] Vo = -38 mV and a = 6.9 mV. The deactivation reciprocal time constant accelerated with hyperpolarization with slope factor 17 mV/e-fold voltage change. 3. The reversal potential for deactivation tail currents varied with external [K+] as if PNa/PK were 0.005. 4. Steady-state current was increased on removing external Ca2+. In the presence of external Ca2+, reactivation of IK(M, ng) after a hyperpolarizing step was delayed. This delay was preceded by an inward Ca2+ current, and coincided with an increase in intracellular [Ca2+] as measured with Indo-1 fluorescence. Elevation of intracellular [Ca2+] with caffeine also reduced IK(M, ng). 5. IK(M, ng) was inhibited by external divalent cations in decreasing order of potency (mM IC50 in parentheses): Zn2+ (0.011) greater than Cu2+ (0.018) greater than Cd2+ (0.070) greater than Ni2+ (0.44) greater than Ba2+ (0.47) greater than Fe2+ (0.69) greater than Mn2+ (0.86) greater than Co2+ (0.92) greater than Ca2+ (5.6) greater than Mg2+ (16) greater than Sr2+ (33). This was not secondary to inhibition of ICa since: (i) inhibition persisted in Ca(2+)-free solution; (ii) La3+ did not inhibit IK(M, ng) at concentrations which inhibited ICa; and (iii) organic Ca2+ channel blockers were ineffective. Inhibition comprised both depression of the maximum conductance and a positive shift of the activation curve. Addition of Ca2+ (10 microM free [Ca2+]) or Ba2+ (1 mM total [Ba2+]) to the pipette solution did not significantly change IK(M, ng). 6. IK(M, ng) was reduced by 9-amino-1,2,3,4-tetrahydroacridine (IC50 8 microM) and quinine (30 microM) but was insensitive to tetraethylammonium (IC50 greater than 30 mM), 4-aminopyridine (greater than 10 mM), apamin (greater than 3 microM) or dendrotoxin (greater than 100 nM). 7. IK(M, ng) was inhibited by bradykinin (1-10 microM) or angiotensin II (1-10 microM), but not by the following other receptor agonists: acetylcholine (10 mM), muscarine (10 microM), noradrenaline (100 microM), adrenaline (100 microM), dopamine (100 microM), histamine (100 microM), 5-hydroxytryptamine (10 microM), Met-enkephalin (1 microM), glycine (100 microM), gamma-aminobutyric acid (100 microM) or baclofen (500 microM).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Kinetic and pharmacological properties of the M-current in rodent neuroblastoma x glioma hybrid cells. 140 9

Lung cytochrome P-450 has been suggested to play a role in hypoxic pulmonary vasoconstriction. We reexamined this hypothesis using specific suicide substrate inhibitors of cytochrome P-450, 1-aminobenzotriazole (1-ABT), and chloramphenicol. In isolated, blood-perfused rat lungs, 1-ABT (0.5 mg/ml) and chloramphenicol (1 mg/ml) inhibited lung microsomal cytochrome P-450 (ethoxycoumarin O-deethylase) activity to 24 and 44% of control, respectively, and blunted hypoxia and angiotensin II-induced vasoconstriction. The depression of vascular contraction by 1-ABT was not due to an effect on calcium channels, since similar concentrations of 1-ABT had no inhibitory activity on electrical field-stimulated contractile response in rabbit papillary muscle strips. However, when 1-ABT was washed out of the lung after preincubation, the vascular reactivity to hypoxia and angiotensin II was restored despite persistent depression of lung cytochrome P-450 activity to 26% of control values. In isolated rat aortic and pulmonary arterial rings, addition of 1-ABT or metyrapone to the organ bath acutely reversed norepinephrine-induced contraction but preincubation with 1-ABT, metyrapone, or chloramphenicol had no effect on subsequent norepinephrine contractions. We conclude that 1-ABT inhibited lung vascular reactivity by a mechanism independent of cytochrome P-450 inhibition or calcium channel blockade and that an intact lung cytochrome P-450 system is not required for hypoxic pulmonary vasoconstriction in rat lungs.
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PMID:Intact lung cytochrome P-450 is not required for hypoxic pulmonary vasoconstriction. 141 22

Agonist challenged aortic prostacyclin production was examined in copper-adequate, -marginal and -deficient rats fed AIN-based diets providing 6.7, 1.7 and 0.8 micrograms Cu/g, respectively. Aortic rings were incubated in Krebs-Henseleit salts, 10 mmol/L HEPES buffer, pH 7.4, 95%:5% O2:CO2, 37 degrees C, and equilibrated for 1 h. Equilibrated rings were challenged with buffer (basal), 273.0 nmol/L thrombin and angiotensin II at 84.6 pmol/L and 846.0 pmol/L. Prostacyclin production, determined at 10 minutes by RIA as 6-keto prostaglandin F1 alpha, in basal and 84.6 pmol/L angiotensin II ring incubations was significantly reduced by 28 to 48% in copper-deficient rats. With thrombin or 846.0 pmol/L angiotensin II prostacyclin production was significantly reduced by 18 to 55% in copper-marginal and copper-deficient rats. Copper-dependent superoxide dismutase activity was significantly depressed by 30 and 57% in aortae of copper-marginal and copper-deficient rats. Lipid peroxidation, estimated by the thiobarbituric acid test, was significantly increased by 85% in copper-deficient rats, with a nonsignificant 40% increase in aortae from copper-marginal rats. The results suggest that the decreases in aortic prostacyclin production in aortae from both copper-deficient and copper-marginal rats are associated, in a dose-dependent manner, with copper-dependent superoxide dismutase depression and increases in aortic lipid peroxidation.
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PMID:Copper-marginal and copper-deficient diets decrease aortic prostacyclin production and copper-dependent superoxide dismutase activity, and increase aortic lipid peroxidation in rats. 143 51

The mechanism underlying the relaxant response of rat aortic rings to the diterpene jatrophone was investigated. Jatrophone (3 and 10 microM) did not affect acetylcholine-induced endothelium-dependent relaxations, but caused concentration-dependent inhibition of noradrenaline (NA)-induced concentrations in unrubbed, and to a lesser extent, in denuded rings. Jatrophone (30 microM) fully prevented responses to angiotensin II and NA, while responses to KCl (up to 220 mM) were unaffected. In depolarizing medium (KCl 40 mM), jatrophone (3-30 microM) antagonized Ca(2+)-induced contractions in a concentration-dependent and noncompetitive manner, while verapamil (10-100 nM) caused a concentration-dependent, rightward displacement and depression of the Ca2+ concentration-response curve. Jatrophone (1 to 300 microM) concentration dependently relaxed rat aortic rings precontraction with either NA (1 microM) or KCl (80 mM), yielding EC50 s of 11 and 24 microM, respectively. These relaxant responses to jatrophone were unaffected by glibenclamide (1 microM), but the concentration-response curve was displaced to the right (2- to 8-fold) by other K+ channel blockers such as tetraethylammonium (10 and 30 mM), 4-aminopyridine (3 and 10 mM) or procaine (1 and 3 mM). These results indicate that jatrophone relaxes the rat aorta, at least in part, by activating K+ channels distinct from the ATP-sensitive subtype. Since jatrophone, like verapamil, relaxed preparations contracted with KCl and inhibited Ca(2+)-induced contractions in depolarized preparations, this diterpene may also block Ca2+ influx through voltage-sensitive channels. However, additional actions of jatrophone on receptor-operated Ca2+ channels causing Ca2+ efflux and/or release cannot be fully ruled out.
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PMID:Analysis of the vasorelaxant action of jatrophone in the isolated aorta of the rat: influence of potassium channel blockers. 151 51

We studied hypoxic pulmonary vasoconstriction (HPV) and pulmonary gas exchange in unanesthetized rats with biliary cirrhosis induced by chronic bile duct ligation (BDL) (5 to 6 wk) and compared pulmonary vascular reactivity in perfused lungs isolated from BDL and control rats. Awake, catheter-implanted, cirrhotic rats exhibited increased cardiac output, normal systemic and pulmonary arterial pressures, and decreased total systemic (TSR) and pulmonary (TPR) vascular resistances in comparison with those in sham-operated control rats. HPV was markedly depressed in cirrhotic rats (percent increase in TPR while breathing 8% O2: 42.3 +/- 13.7% in control and 0.9 +/- 3.6% in cirrhotic rats, p less than 0.05), and this was associated with an increased AaPO2 (control rats, 15.7 +/- 1.1 mm Hg; cirrhotic rats, 23.1 +/- 1.9 mm Hg; p less than 0.05). In contrast, the pulmonary pressor response to angiotensin II was intact, and the depression of HPV in cirrhotic rats was ameliorated after angiotensin II infusion. These changes in cirrhotic rats were not due to the accompanying cholestasis since noncirrhotic rats with severe cholestasis had intact HPV and normal AaPO2. Lungs isolated from cirrhotic rats and perfused with blood from normal rats exhibited two patterns of response to hypoxia. In one group, HPV was blunted compared with that in control rats (change in pulmonary arterial perfusion pressure after 3% O2: control rats, 23.2 +/- 2.8 mm Hg; cirrhotic rats, 4.8 +/- 1.4 mm Hg; p less than 0.01). Similar to the result in intact rat, angiotensin-II-induced vasoconstriction was preserved in lungs from cirrhotic rats, and HPV increased significantly after angiotensin II infusion (to 17.3 +/- 4.8 mm Hg). In the second group, baseline pulmonary arterial pressure progressively increased during normoxia, and this increase was attenuated by hypoxic ventilation (hypoxic vasodilation).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary circulatory dysfunction in rats with biliary cirrhosis. An animal model of the hepatopulmonary syndrome. 155 5

It has been reported that after 40 minutes of stimulation of the medullary reticular formation (MORF), widespread significant increase by 1.4% to 2.8% in brain water content occurs in white matter of the injured hemisphere. Recent studies indicate that centrally released arginine vasopressin (AVP) influences water permeability of the brain in both normal and pathological conditions. The present study was carried out to clarify the effect of electrical stimulation of MORF on centrally released AVP. The cats were divided into three groups. In group A (16 cats), electrical stimulation of MORF (1msec, 5V, 50Hz) was carried out for 80 minutes in normal cats. In group B (11 cats), stimulation was started 17 hours after cold injury under the same conditions and carried out for 80 minutes. In group C (10 cats), angiotensin II was administered to elevate blood pressure to the same degree as during MORF stimulation 17 hours after cold injury. AVP concentrations in the cerebrospinal fluid (CSF), plasma and brain tissue of the injured and non-injured white matter were measured by radioimmunoassay. Plasma osmolality was also determined by the freezing point depression method. Normal values (mean +/- S. D.) of CSF and plasma AVP were 4.0 +/- 2.2 and 9.9 +/- 3.6 pg/ml respectively. Plasma AVP and osmolality did not show significant changes before and at the end of experiments in all groups. There were no significant changes in CSF AVP by induced hypertension for 80 minutes (Group C). Stimulation of the medullary reticular formation resulted in significant and progressive increase in CSF AVP in normal and injured brain (Group A, B).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Changes in centrally released arginine vasopressin by stimulation of the medullary reticular formation]. 156 84

The pharmacological effects of angiotensin II (AII) are potently inhibited by several peptide and recently synthesized nonpeptide AII receptor antagonists. The interaction of sarcosine1, isoleucine8-AII (sarile), sarcosine1,O-methyltyrosine4-AII (sarmesin), and the nonpeptide AII antagonists 2-n-butyl-4-chloro-5- hydroxymethyl-1-[(2'-(1H-tetrazole-5-yl)biphenyl-4-yl)- methyl]imidazole (DuP 753, Losartan potassium) and its metabolite 2-n-butyl-4-chloro-1-[(2'-(1H-tetrazole-5-yl)biphenyl-4-yl)methyl]imidaz ole - 5-carboxylic acid (EXP3174) with AII binding sites was investigated in radioligand binding and functional studies. Sarile, sarmesin, DuP 753, and EXP3174 inhibited 125I-AII binding to rat lung tissue, with Ki values of 3.5, 16.1, 23.7, and 10.4 nM, respectively. The Hill coefficients of all displacement curves, except for sarile (nH, 1.45), were not significantly different from unity. In functional experiments using rabbit aorta, sarmesin and DuP 753 competitively inhibited the contractile response to AII, with pA2 values of 6.75 and 8.01, respectively. Sarile, in contrast, revealed noncompetitive antagonism, i.e., the maximum contractile force and the slope of the concentration-contractile force curve were significantly and concentration-dependently depressed. The concentration-contractile response curve for AII was shifted to the right in a parallel fashion in the presence of EXP3174 (3 nM to 1 microM); however, the maximum contractile force was significantly decreased, by 24%. The marked noncompetitive antagonism of sarile (3 nM) was reversed in the presence of increasing concentrations of sarmesin (30 nM to 30 microM) or DuP 753 (10 nM to 1 microM), whereas in the presence of increasing concentrations of EXP3174 (3-300 nM) a 25% depression in maximum contractile force persisted. Moreover, the reduction of the maximum contractile force by EXP3174 (10 nM) was concentration-dependently restored in the presence of increasing concentrations of DuP 753 (10 nM to 1 microM), indicating interaction with the same binding site. Whereas sarile (0.3-10 nM) did not affect the 125I-AII binding capacity in radioligand saturation experiments, a 54% reduction of Bmax was observed in the presence of 100 nM EXP3174. The data provide evidence that all antagonists inhibit the functional response to AII by interacting with a common binding site at the receptor. The noncompetitive behavior of sarile seems to be due to slow dissociation from this receptor site. An additional mechanism must be postulated for EXP3174. An allosteric interaction with the receptor, as suggested by the reduction in Bmax, may be, at least in part, responsible for the nonclassical antagonism of this compound.
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PMID:Different types of receptor interaction of peptide and nonpeptide angiotensin II antagonists revealed by receptor binding and functional studies. 161 10

The vasorelaxing and dihydropyridine receptor binding properties of NZ-105, a new dihydropyridine derivative, were studied using isolated rabbit aorta, and compared with those of nicardipine, nifedipine and diltiazem. NZ-105 (3 x 10(-10)-3 x 10(-9) M), nicardipine (3 x 10(-10), 10(-9) M), and diltiazem (3 x 10(-7), 10(-6) M) selectively relaxed aortic strips precontracted with high-K+ solution (50 mM) with little effect on strips precontracted with phenylephrine (10(-5) M) or clonidine (10(-6) M). The relaxation produced by NZ-105 was of very slow onset, and no recovery was observed after a 2 hr washout with high-K+ or normal bathing solution. NZ-105 (3 x 10(-10)-3 x 10(-9) M) caused a non-parallel depression of the concentration-response curve for the CaCl2-induced contraction in high-K(+)-depolarized rabbit aorta, whereas nicardipine (10(-10), 3 x 10(-10) M), nifedipine (10(-9), 3 x 10(-9) M) and diltiazem (10(-7), 3 x 10(-7) M) all produced a concentration-related rightward displacement of the curve. The depression induced by NZ-105, but not by nicardipine, became greater as the period of preincubation with the drug was prolonged. NZ-105, nicardipine and diltiazem, at the very high concentration of 10(-6) M, caused a slight and noncompetitive inhibition of the concentration-response curves for norepinephrine, prostaglandin F2 alpha, angiotensin II and 5-hydroxytryptamine. NZ-105 displaced 3H-nitrendipine binding to rabbit aortic membranes in a manner similar to that of nicardipine and nifedipine, and this was also incubation time-dependent. These results indicate that NZ-105 possesses selective calcium antagonist properties, with respect to the rabbit isolated vascular smooth muscle, which are of very slow onset and long-lasting. The slow onset of the vasorelaxation may be due to a slow association rate to dihydropyridine receptors. These pharmacological properties of NZ-105 may, at least in part, be responsible for the slow onset and long duration of its antihypertensive action in vivo.
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PMID:Vasorelaxing and receptor binding properties of NZ-105, a novel dihydropyridine derivative, in isolated rabbit aorta. 166 36

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