Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II inhibits nonadrenergic (purinergic) neurotransmission in the vas deferens and potentiates adrenergic neurotransmission and prostaglandin (PG)E synthesis. Other angiotensin responses are sensitive to either dithiothreitol or pertussis toxin. The present study tested the hypothesis that dithiothreitol or pertussis toxin selectively depress angiotensin responses in the vas deferens. The dithiothreitol (10 mM) eliminated the potentiation of both adrenergic neurotransmission and PGE synthesis but did not alter the depression of purinergic neurotransmission. In contrast, pertussis toxin (100 ng/ml for 3 hr) eliminated the depression of purinergic neurotransmission but had no effect on adrenergic neurotransmission or PGE synthetic responses to angiotensin II. The results are consistent with the existence of at least two transduction pathways for angiotensin II, one enhancing adrenergic neurotransmission and PGE synthesis and the other depressing purinergic neurotransmission. The results indicate that the vas deferens is a useful preparation in defining selective actions of angiotensin receptor agonists or antagonists.
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PMID:Pharmacological differentiation of angiotensin effects in the rabbit isolated vas deferens with dithiothreitol and pertussis toxin. 215 55

We examined the effect of two angiotensin receptor antagonists on neuromodulatory and prostaglandin-producing effects of angiotensin II in the rabbit isolated vas deferens because prior studies have established that angiotensins selectively influence the two neural events, one being adrenergic and the other nonadrenergic. Angiotensin II increased adrenergic neurotransmission and prostaglandin E synthesis in a concentration-dependent manner while depressing nonadrenergic neurotransmission. The [1-Sarcosine, 8-Alanine]-angiotensin II preferentially antagonized adrenergic neuromodulatory effects of angiotensin II. In contrast, the nonadrenergic neuromodulatory and prostaglandin E-releasing effects of angiotensin II were suppressed by [1-Sarcosine, 8-Alanine]-angiotensin II to a lesser extent. The nonpeptide angiotensin receptor antagonist, Dupont 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2(1)-(1-H-tetrazol-5-yl) biphenyl-4-yl)methyl] imidazole, potassium salt, exhibited the opposite selectivity. It eliminated the depression of nonadrenergic neurotransmission without significantly altering the potentiation of adrenergic neurotransmission caused by angiotensin II. The angiotensin-induced stimulation of prostaglandin E synthesis was also eliminated by this antagonist. These data suggest that angiotensin effects in the vas deferens are mediated by at least two types of angiotensin receptors.
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PMID:Selective blockade of angiotensin responses in the rabbit isolated vas deferens by angiotensin receptor antagonists. 226 11

The role of prostaglandins in mediating angiotensin effects on autonomic neurotransmission was assessed. This was accomplished by examining the angiotensin-induced production of prostaglandins (PGE) and suppression of non-adrenergic (purinergic) neurotransmission in the presence and absence of cyclo-oxygenase inhibitors. The vas deferens of the rabbit was utilized for these studies because this preparation has a predominant non-adrenergic neurogenic component. Both angiotensins II and III enhanced PGE production and reduced non-adrenergic neurogenic contractions in a concentration-dependent manner from 1 to 1000 nM. Furthermore, indomethacin (2.8 microM) and eicosatetraynoic acid (10 microM) eliminated the inhibitory effect of the angiotensins on non-adrenergic neurotransmission. However, acetylsalicylic acid (10 microM) prevented the production of PGE in response to the angiotensins but failed to alter the suppression of non-adrenergic neurotransmission. The latter data are inconsistent with the hypothesis that PG's mediate angiotensin-induced depression of non-adrenergic neurotransmission. The mechanism by which indomethacin and eicosatetraynoic acid prevent angiotensin effects on non-adrenergic neurotransmission was not elucidated but previous reports suggest that these agents may act as angiotensin receptor antagonists. All of the cyclo-oxygenase inhibitors examined tended to potentiate angiotensin effects on adrenergic neurotransmission.
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PMID:Prostaglandins do not mediate the inhibitory effects of angiotensins II and III on autonomic neurotransmission in the rabbit vas deferens. 284 51

A previously reported depression of glutamate responses by angiotensin II was investigated to define the nature of this neuromodulatory effect. Studies were carried out in an vitro brain slice preparation containing the locus coeruleus, using intracellular recordings, and iontophoretic, micropressure and bath perfusion methods for application of drugs. The angiotensin action was found to be blocked by a non-peptide antagonist specific for the angiotensin type 2 receptor, and not by an antagonist selective for the type 1 receptor. Excitatory postsynaptic potentials mediated primarily by excitatory amino acids were also depressed by angiotensin II. The angiotensin II depressions of glutamate were shown to be strong and highly specific. The low effectiveness of bath-applied compared with iontophoretically or micropressure-applied angiotensin II was found to be at least partly explained by a rapid degradation by peptidases. Ammonium ions and hydrogen ions were also able to depress glutamate responses, but these effects were not specific for locus coeruleus neurons and were mediated independently of the angiotensin actions. Strong depression by angiotensin II of excitatory postsynaptic potentials as well as exogenously applied glutamate strengthens the strong possibility of a physiological role for this neuromodulatory mechanism. The identification of the type 2 angiotensin receptor subtype as the mediator of this effect indicates a novel functional role for this receptor, since previously recognized functions of angiotensin II in the brain, such as vascular and body fluid regulation, have been associated with the type 1 receptor.
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PMID:Angiotensin II depresses glutamate depolarizations and excitatory postsynaptic potentials in locus coeruleus through angiotensin II subtype 2 receptors. 781 98

The brain renin-angiotensin system (RAS), which is comprised of a variety of peptides including angiotensin II, angiotensin III and angiotensin IV acting on AT<inf>1</inf>, AT<inf>2</inf> and AT<inf>4</inf> receptors, is important in cognition and anxiety. Perturbation of the RAS improves basal cognition and reverses age-, scopolamine-, ethanol- and diabetes-induced deficits. In studies of dementias and Alzheimer's disease (AD), some studies have shown that antihypertensive drugs, including angiotensin-converting enzyme inhibitors, have some moderate effects on cognitive decline, but that the angiotensin receptor antagonist losartan has a significantly beneficial effect. These findings suggest that angiotensin receptor ligands may have potential in the prevention or even reversal of vascular dementias and AD. With respect to depression and anxiety, there is similar experimental evidence from animal models that drugs acting on the RAS may be antidepressant or anxiolytic, but insufficient clinical data exist. Such effects, if proven, could promote the use of such agents in the treatment of hypertension coexisting with depression or anxiety.
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PMID:Angiotensin as a target for the treatment of Alzheimer's disease, anxiety and depression. 1499 14

In order to understand the mechanisms of exercise intolerance and muscle fatigue, which are commonly observed in congestive heart failure, we studied sarcoplasmic reticulum (SR) Ca(2+)-transport in the hind-leg skeletal muscle of rats subjected to myocardial infarction (MI). Sham-operated animals were used for comparison. On one hand, the maximal velocities (Vmax) for both SR Ca(2+)-uptake and Ca(2+)-stimulated ATPase activities in skeletal muscle of rats at 8 weeks of MI were higher than those of controls. On the other hand, the Vmax values for both SR Ca(2+)-uptake and Ca(2+)-stimulated ATPase activities were decreased significantly at 16 weeks of MI when compared with controls. These alterations in Ca(2+)-transport activities were not associated with any change in the affinity (1/Ka) of the SR Ca(2+)-pump for Ca2+. Furthermore, the stimulation of SR Ca(2+)-stimulated ATPase activity by cyclic AMP-dependent protein kinase was not altered at 8 or 16 weeks of MI when compared with the respective control values. Treatment of 3-week infarcted animals with angiotensin-converting enzyme (ACE) inhibitors such as captopril, imidapril, and enalapril or an angiotensin receptor (AT1R) antagonist, losartan, for a period of 13 weeks not only attenuated changes in left ventricular function but also prevented defects in SR Ca(2+)-pump in skeletal muscle. These results indicate that the skeletal muscle SR Ca(2+)-transport is altered in a biphasic manner in heart failure due to MI. It is suggested that the initial increase in SR Ca(2+)-pump activity in skeletal muscle may be compensatory whereas the depression at late stages of MI may play a role in exercise intolerance and muscle fatigue in congestive heart failure. Furthermore, the improvements in the skeletal muscle SR Ca(2+)-transport by ACE inhibitors may be due to the decreased activity of renin-angiotensin system in congestive heart failure.
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PMID:Changes in skeletal muscle SR Ca2+ pump in congestive heart failure due to myocardial infarction are prevented by angiotensin II blockade. 1538 90

Hyperkalemia is a complications of the use of angiotensin converting enzyme inhibitors, angiotensin receptor antagonists and aldosterone antagonists. These drugs are commonly used for the treatment of hypertension and cardiac failure. We report a 84 year-old female treated with losartan 50 mg/day and spironolactone 25 mg/day that presented with a hyperkalemia of 8.4 mEq/l and bradicardia, drowsiness and respiratory depression. She required hemodialysis and ventilatory assistance. She was discharged in good conditions five days after admission.
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PMID:[Severe hyperkalemia associated to the use of losartan and spironolactone: case report]. 1616 34

The issue of drug-drug interactions is particularly relevant for geriatric patients with epilepsy because they are often treated with multiple medications for concurrent diseases such as cardiovascular disease and psychiatric disorders (e.g., dementia and depression). The antidepressants with the least potential for altering antiepileptic drug (AED) metabolism are citalopram, escitalopram, venlafaxine, duloxetine, and mirtazapine. The use of established AEDs with enzyme-inducing properties, such as carbamazepine, phenytoin, and phenobarbital, may be associated with reductions in the levels of drugs such as donepezil, galantamine, and particularly warfarin. Carbamazepine, phenytoin, and phenobarbital have been reported to decrease prothrombin time in patients taking oral anticoagulants, although with phenytoin, an increase in prothrombin time has also been reported. Drugs associated with increased risk of bleeding in patients taking oral anticoagulants include selective serotonin reuptake inhibitors (especially fluoxetine), gemfibrozil, fluvastatin, and lovastatin. Other drugs affected by enzyme inducers include cytochrome P450 3A4 substrates, such as calcium channel blockers (e.g., nimodipine, nilvadipine, nisoldipine, and felodipine) and the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors atorvastatin, lovastatin, and simvastatin. Although there have been no reports of AEDs altering ticlopidine metabolism, ticlopidine coadministration can result in carbamazepine and phenytoin toxicity. Also, there is a significant risk of elevated levels of carbamazepine when diltiazem and verapamil are administered. In addition, there are case reports of phenytoin toxicity when administered with diltiazem. Drugs with a lower potential for metabolic drug interactions include (1) cholinesterase inhibitors (although the theoretical possibility of a reduction in donepezil and galantamine levels by enzyme-inducing AEDs should be considered) and the N-methyl-D-aspartate receptor antagonist memantine and (2) antihypertensives such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, hydrophilic beta-blockers, and thiazide diuretics. There is a moderate risk that enzyme-inducing AEDs will decrease levels of lipophilic beta-blockers. Newer AEDs have a lower potential for drug interactions. In particular, levetiracetam and gabapentin have not been reported to alter enzyme activity. In summary, there is a significant potential for drug interactions between AEDs and drugs commonly prescribed in geriatric patients with epilepsy.
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PMID:Risk and predictability of drug interactions in the elderly. 1743 28

Given the abundance of the renin-angiotensin system (RAS) components in the brain, their importance in behavior and cognition, and the data that implicates them in the etiology and treatment of depression, it is possible that those RAS gene polymorphisms associated with increased RAS activity may also be associated with depression. The frequencies of common polymorphisms of genes encoding for components of the RAS, namely angiotensinogen (M235T), angiotensin converting enzyme (ACE) (insertion, I; deletion, D), angiotensin receptor type I (A1166C), and angiotensin receptor type II (C3123A) were determined in DNA extracted from buccal cells from a Lebanese population of 132 depressed patients and their first-degree relative case-controls. The angiotensin receptor type 1 (A1166C) CC genotype was significantly associated with depression (p=0.036). None of the other common RAS-associated polymorphisms were significantly associated. The results support the hypothesis that increased RAS activity may increase relative risk of depression in that the angiotensin receptor type 1 (A1166C) CC genotype is associated with increased responsiveness to angiotensin II.
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PMID:Renin-angiotensin-system gene polymorphisms and depression. 1749 13

Diabetes mellitus type 2 (DM type 2) is associated with depressive symptomatology and intermittent hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis. DM type 2 is also accompanied by increased tissue levels of angiotensin II (Ang II), which stimulates the HPA axis through the Ang II type 1 receptors (AT1). We investigated the effect of candesartan, an angiotensin receptor blocker (ARB) that crosses the blood brain barrier, on the activity of the HPA axis and on the affect of 17 patients with DM type 2, aged 40-65 years, who were treated with 4 mg/day candesartan per os for at least 3 months. Before and after candesartan administration, a corticotropin-releasing hormone (CRH) stimulation test and psychological tests were performed. In response to hCRH, time-integrated secretion of ACTH was not altered by candesartan administration, however, the cortisol response was decreased significantly compared to baseline (mean +/- SEM, 2327 +/- 148.3 vs. 1943 +/- 131.9 microg/dl, P = 0.005) suggesting reduced sensitivity of the adrenals to ACTH. In parallel, there was a significant improvement in interpersonal sensitivity (0.91 +/- 0.16 vs. 0.70 +/- 0.15, P = 0.027) and depression scores (0.96 +/- 0.15 vs. 0.71 +/- 0.10, P = 0.026). We suggest that candesartan resets the HPA axis of patients with DM type 2 and improves their affect.
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PMID:Chronic administration of an angiotensin II receptor antagonist resets the hypothalamic-pituitary-adrenal (HPA) axis and improves the affect of patients with diabetes mellitus type 2: preliminary results. 1785 61


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