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)

The conventional "stepped-care" approach to the treatment of hypertension deserves revision. Rational therapy considers a variety of factors to obtain maximum efficacy, safety, tolerability, compliance, and neutralization of neural tone for the prevention of sudden death. The patient's age, gender, race, behavior profile, hemodynamic and neurohumoral status (plasma renin activity, norepinephrine/epinephrine ratio), and quality of life will help determine the choice of antihypertensive agent. Concomitant risk factors (smoking, obesity, diabetes, hypercholesterolemia), the presence of sequelae (left ventricular hypertrophy and/or failure, renal failure), and the existence of other disorders (mitral valve prolapse, depression, anxiety) must also be considered when initiating treatment. In addition, the cost of ancillary expenses (laboratory tests, hospitalizations, and emergency room visits) must be weighed against the potential benefits of therapy. Beta blockers are effective, well tolerated, and versatile for the treatment of concomitant cardiovascular disorders and as behavior modifiers. Calcium channel blockers and angiotensin converting enzyme inhibitors also show promise and merit consideration as therapy for specific groups of hypertensive patients.
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PMID:The 1980s: a patient-specific therapeutic approach in hypertension. 288 36

Angiotensin converting-enzyme inhibitors cross the placenta and modify the maternal, foetal and utero-placental renin-angiotensin system. Eight cases of pregnancy in women taking captopril have been published, 7 other cases being reported in this review paper. There were one spontaneous and 2 therapeutic abortions, one of which disclosed a malformation of uncertain diagnosis and imputation. One intrauterine death at 28 weeks was probably due to the severity of the maternal disease. Two children born to mothers also treated with frusemide died of neonatal anuria. Delivery or caesarean section occurred before term in 8 cases, and there were 3 cases of neonatal respiratory distress with a favourable outcome. Finally, one mother gave birth at term to twins of normal weight. The cases with respiratory distress can be attributed to the mother's hypertension, to prematurity and/or to concomitant treatment with beta-blockers, while the cases with anuria seem to be due to inhibition of the effects of angiotensin on renal haemodynamics, with salt depression as a possible aggravating factor. Treatment with angiotensin converting enzyme inhibitors does not seem to warrant therapeutic abortion. However, these drugs are contra-indicated in pregnancy and should only be given to women wishing to become pregnant if they present with resistant and dangerous arterial hypertension. A programme of pharmacovigilance is being set up to follow up such pregnancies.
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PMID:[Inhibition of angiotensin converting enzyme in human pregnancy. 15 cases]. 300 90

Oral angiotensin converting enzyme inhibition was introduced eight years ago and is becoming increasingly popular for the treatment of hypertension and congestive heart failure. This treatment causes blood pressure lowering associated with suppression of angiotensin and aldosterone, lack of orthostatic hypotension or metabolic disturbances, redistribution of regional blood flows in favor of vital organs and, in the long term, decreased sympathetic drive and regression of left ventricular hypertrophy. It is effective as monotherapy in more than 50 percent of unselected patients; addition of a diuretic increases the percentage of responders to more than 80 percent. It is the treatment of choice for patients with concurrent diabetes, asthma, gout, depression, or very active life-style. Side effects, observed originally in patients with severe hypertension and renal failure treated with very high doses of captopril, are rare in otherwise healthy hypertensive patients receiving smaller doses of this drug and virtually absent with second-generation angiotensin converting enzyme inhibitors like enalapril.
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PMID:Clinical utility of angiotensin converting enzyme inhibitors in hypertension. 302 82

(2R,4R)-2-(o-Hydroxyphenyl)-3-(3-mercaptopropionyl)-4- thiazolidinecarboxylic acid (rentiapril, SA 446), an orally active inhibitor of angiotensin converting enzyme, was examined for effects upon general reproductive performance, for embryofoetal toxicity and for peri- and postnatal toxicity in the rat at dosages of 0, 20, 100 and 500 mg/kg/d. Embryofoetal toxicity was also examined in the New Zealand White rabbit at dosages of 0, 1, 2 and 4 mg/kg/d. The compound was administered by gastric intubation. Prolonged treatment at 100 and 500 mg/kg/d during the fertility study was associated with some slight depression of body weight gain of males. Body weight gain of females during gestation was significantly depressed at 500 mg/kg/d. There was salivation in both sexes at 500 mg/kg/d and also in males receiving 100 mg/kg/d. Following this prolonged treatment in the fertility study. Fo male and female kidney weights were increased at all dosages. Although there was no obvious effect upon fertility there was an increased incidence of total litter loss at 500 mg/kg/d and mean pup weights to day 21 post partum were reduced at this dosage and at 100 mg/kg/d with delays in the attainment of some of the developmental landmarks. In the rat treatment at 500 mg/kg/d from day 7 to 17 of pregnancy did not adversely effect embryofoetal development. Subsequent development and reproductive performance of the F1 offspring was also unimpaired. During this treatment period signs of salivation were seen at 500 mg/kg/d. Slight retardation of maternal body weight gain was noted at 500 mg/kg/d and at 100 mg/kg/d but not at 20 mg/kg/d.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reproductive toxicity studies of rentiapril. 303 99

Since their introduction in clinical practice in 1980, ACE inhibitors have been found useful in the treatment of hypertension and CHF. In hypertension, they are effective as monotherapy in 40% to 50% of the patients, and in combination with diuretics or calcium antagonists, they are effective in up to 85% of the patients. They are well tolerated, are not associated with depression, impotence, bronchospasm or metabolic derangements such as hypokalemia, hyperuricemia or hyperglycemia, and do not have adverse effects on the quality of life. As a result, they are preferred in hypertensive patients with CHF, left ventricular dysfunction, mental depression, older age, coronary artery disease, metabolic disorders, chronic destructive pulmonary disease, and peripheral vascular disease. In CHF they cause long-lasting hemodynamic and symptomatic improvement, improve exercise tolerance, and may lower mortality in certain patient subsets. Evolving new indications for ACE inhibitors include the diagnosis of renovascular hypertension, the prediction of surgical success, the treatment of scleroderma renal crisis, the reduction of proteinuria, renal protection, cardioprotection, the improvement of arterial compliance, in Bartter's syndrome and idiopathic edema, etc. ACE inhibitors are usually well tolerated but in some instances they may cause class-specific side effects such as hypotension; usually reversible azotemia or renal failure, especially in patients with renal artery stenosis or with CHF with low blood pressure; cough; angioedema; and hyperkalemia. Differences among ACE inhibitors are emerging and include chemical class (e.g., zinc ligand), biotransformation, potency, pharmacokinetics, prodrugs, tissue effects, additional pharmacologic properties, and drug interactions.
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PMID:Angiotensin converting enzyme inhibitors. II. Clinical use. 305 46

We have utilized several inhibitors to assess the effects of kininases on the contractile activity of bradykinin (BK), kallidin (KD), des-Arg9-BK and des-Arg10-KD on two isolated blood vessels, the rabbit aorta and mesenteric vein. The response of the two vessels to kinins are mediated by B1-receptors, implying that fragments of kinins without the C-terminal arginine are much more active on these tissues than the whole kinin sequences. Blockers of carboxypeptidase B-like enzymes, such as SQ24798 and pivalyl-L-arginine decrease the apparent affinity of BK and KD on the two vessels, while not changing those of des-Arg9-BK and des-Arg10-KD; this suggests that a major part of the contractile activities of BK and KD are mediated by des-Arg metabolites formed in situ at the tissue level by a kininase I. The block of kininase II by captopril or desacetylated MK-421 bring about a complex pattern of activity changes that include the potentiation of BK and KD and the depression of des-Arg10-KD. These results, in conjunction with those obtained with the non-specific inhibitors of metallopeptidases, thioglycolic acid and EDTA, suggest that the relative contribution of kininase I and kininase II to the degradation of kinins in arterial and venous vessels may be different. The implications of these findings on the pharmacology of B1-receptors are discussed.
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PMID:Kininases and vascular responses to kinins. 612 86

Earlier studies by other investigators have shown that acute exposure of cultured endothelial cells to hypoxic atmospheres inhibits the activity of the angiotensin converting enzyme in situ, resulting in severe but reversible depression of the rate of degradation of bradykinin. We exposed primary cultures of endothelial cells from the pulmonary artery of the pig to a range of hypoxic gas mixtures and measured the activity of the angiotensin converting enzyme in situ using angiotensin I as substrate. Each cell flask was exposed in random sequence to both hypoxic gas mixtures (PO2 29-69 torr) and room air for 40 min in Dulbecco's medium containing angiotensin I at concentrations of 1000 (N = 7), 500 (N = 8) or 100 ng/ml (N = 4). Angiotensin I disappearance rates and angiotensin II generation rates were linear. Recovery of immunoreactive peptide as either angiotensin I or II following 40 min of incubation was 86 +/- 17% (S.D.). The rate of increase in angiotensin II concentration in surface medium in room air experiments was 91 +/- 51 (S.D.) ng x ml-1 x hr-1. During hypoxia it was 85 +/- 42 ng x ml-1 x hr-1. The difference in rates was not significant by paired t analysis. The results of this study are consistent with earlier observations by the authors which suggest that hypoxia-induced depression of angiotensin I conversion in vivo is due to hemodynamic phenomena. Further studies are needed to clarify the role of cellular mechanisms in hypoxia-induced depression of angiotensin metabolism.
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PMID:Effect of hypoxia on the conversion of angiotensin I to II in cultured porcine pulmonary endothelial cells. 630 52

Serum angiotensin-converting enzyme activity (s-ACE) was measured spectrophotometrically in a variety of renal disorders. In 111 renal patients not on dialysis, s-ACE was slightly lower (22.9 +/- 5.9 U/ml; mean +/- SD) than in 116 controls 24.4 +/- 6.2 U/ml). In 52 patients on chronic hemodialysis s-ACE was 24.1 +/- 4.7 U/ml; serial analyses done before initiation of chronic dialysis showed a significant increase in s-ACE levels towards normal values. In 38 renal allograft recipients s-ACE was relatively low (22.0 +/- 5.0 U/ml); a significant decrease in s-ACE was observed in patients followed from the time of transplantation (24.6 +/- 6.4 U/ml) to two weeks after transplantation (20.2 +/- 4.5 U/ml). S-ACE was also depressed (17.4 +/- 2.6 U/ml) in 12 patients with acute renal failure, and it increased in parallel with normalization of renal function. S-ACE was normal (24.4 +/- 5.7 U/ml) in 14 patients with essential hypertension. Elevated s-ACE (above mean of controls + 2 SD) was observed in only one patient of the total series. We could not confirm previous reports on elevated s-ACE in dialysis patients, but several factors invalidate a direct comparison between series. Thus, the deviations in s-ACE in renal disorders seem to be discrete: depressed levels in acute renal failure and a relative depression in undialyzed patients with chronic renal disorders. The low activity after transplantation may be secondary to the immunosuppressive treatment.
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PMID:Angiotensin-converting enzyme activity in renal disorders: influence of disease pattern, hemodialysis and transplantation. 632 76

The Warburg method was used to study the action of adenosine on several phases of rat cerebral cortex metabolism, using cortex slices or homogenates. In the presence of exogenous glucose in vitro, oxygen consumption and lactate production are not affected by adenosine in sections. In vivo, there is an increase of oxygen consumption and of lactate production but which are not significant. Adenosine may activate metabolic pathways, since the observed metabolic changes remain constant during the period of activity of adenosine (30 to 60 min) and disappear concomitantly with adenosine. The action of adenosine is much more evident in sections from the brains of injected animals, where the increase of lactate production becomes significant. This suggests that in this case adenosine favors a better utilization of glycogen via an activation of adenylate cyclase. The increased activity of G-6-PDH was observed in vitro but was not significant in vivo. These observations were confirmed with homogenates from the in vivo series by the significant decrease of inorganic phosphate levels, consistent with an increased formation of nucleotide phosphates. The increased cerebral glucose concentration is perhaps a result of increased blood glucose levels, in turn resulting from the known depression of insulin release by adenosine, or from a preferential utilization of glycogen, resulting from the activation of adenylate cyclase.
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PMID:Action of adenosine on energy metabolism and on glucose-6-phosphate dehydrogenase in rat brains. 672 44

The effect of acute administration of captopril, an angiotensin converting enzyme inhibitor, on vascular responses of rings of rat aortic smooth muscle was tested in vitro. Dose-response curves for various vasoactive agents were obtained before and after exposure to captopril (2 x 10(-4) M) for 30 minutes. In the presence of captopril, contractile responses to angiotensin I (5 x 10(-10) to 5 x 10(-8) M) were attenuated significantly, probably as a result of decreased local conversion of angiotensin I to angiotensin II. Contractile responses to angiotensin II (10(-11) to 5 x 10(-9) M) were not affected by captopril. All responses to norepinephrine (10(-9) to 10(-4) M) and phenylephrine (10(-8) to 10(-4) M) were attenuated significantly from control in the presence of captopril. In the presence of the alpha-adrenergic antagonist, phentolamine, captopril did not affect either the contractile responses to KCl (30 to 100 mM) or the isoproterenol-induced (10(-8) to 10(-5) M) relaxation of KCl-depolarized tissue. These results suggest that captopril decreased vascular responsiveness to alpha-adrenergic agonists but not to beta-adrenergic agonists. Low concentrations of bradykinin (10(-10) to 10(-8) M) induced contraction in KCl-depolarized tissue while higher concentrations (10(-7) and 10(-6) M) induced relaxation. In the presence of captopril, relaxation occurred at all concentrations of bradykinin (10(-10) to 10(-6) M), probably as a result of decreased degradation of the bradykinin. These data suggest depression of alpha-adrenergic responsiveness in vascular smooth muscle as another potential antihypertensive action of captopril.
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PMID:Effect of in vitro administration of captopril on vascular reactivity of rat aorta. 703 33


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