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)

Spontaneously hypertensive rats (SHR) of advanced age exhibit depressed myocardial contractile function and ventricular fibrosis, as stable compensated hypertrophy progresses to heart failure. Transition to heart failure in SHR aged 18-24 months was characterized by impaired left ventricular (LV) function, ventricular dilatation, and reduced ejection fraction without an increase in LV mass. Studies of papillary muscles from SHR with failing hearts (SHR-F), SHR without failure (SHR-NF), and age-matched Wistar Kyoto (WKY) rats allowed examination of changes in the mechanical properties of myocardium during the transition to heart failure. Papillary muscles of SHR-F exhibited increased fibrosis, impaired contraction, and decreased myocyte fractional area. These findings in papillary muscles were correlated with a higher concentration of hydroxyproline and increased histological evidence of fibrosis in the LV free wall. While a depression in active tension accompanied these structural alterations in papillary muscles, it was not evident when active tension was normalized to myocyte fractional area. Together, these data suggest that individual myocyte function may be preserved but that myocyte loss and replacement by extracellular matrix contribute substantially to the decrement in active tension. An absent or negative inotropic response to isoproterenol is observed in SHR-F and SHR-NF papillary muscles and may result in part from age-related alterations in beta-adrenergic receptor dynamics and a shift from alpha- to beta-myosin heavy chain (MHC) protein. During the transition to failure, ventricles of SHR exhibit a marked increase in collagen and fibronectin mRNA levels, suggesting that an increase in the expression of specific extracellular matrix genes may contribute to fibrosis, tissue stiffness, and impaired function. Transforming growth factor-beta 1 (TGF-beta 1) mRNA levels also increase in SHR-F, consistent with the concept that TGF-beta 1 plays a key regulatory role in remodelling of the extracellular matrix gene during the transition to failure. The renin-angiotensin-aldosterone system is also implicated in the transition to failure: SHR treated with the angiotensin converting enzyme inhibitor captopril starting at 12 months of age did not develop heart failure during the 18-24 month observation period. Captopril treatment that was initiated after rats were identified with evidence of failure led to a reappearance of alpha-MHC mRNA but did not improve papillary muscle function. Research opportunities include investigation of apoptosis as a mechanism of cell loss, delineation of the regulatory roles of TGF-beta 1 and the renin-angiotensin-aldosterone system in matrix accumulation, and studies of proteinase cascades that regulate matrix remodelling.
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PMID:The ageing spontaneously hypertensive rat as a model of the transition from stable compensated hypertrophy to heart failure. 868 57

In untreated congestive heart failure, aldosterone plasma concentrations are elevated in proportion to the severity of the disease and are further increased by the use of diuretic treatment. Angiotensin II, plasma potassium concentration, and corticotropin are the major stimulators of aldosterone synthesis. During angiotensin converting enzyme (ACE) inhibition, the role of alternative major or minor regulatory mechanisms may become significant. This may explain why during continuous ACE inhibition, after an initial reduction, plasma aldosterone measurements may subsequently increase to pretherapeutic levels. In addition to causing sodium and water retention, aldosterone contributes to hypokalaemia and hypomagnesaemia, which may induce electrical instability and death of cardiac myocytes. Aldosterone is also one factor involved in cardiac hypertrophy and fibrosis, which, together with myocardial cell death, may underlie progressive adverse myocardial remodelling. Evidence for a direct vascular effect of aldosterone suggests that this hormone may contribute to generalized vasoconstriction. Elevated plasma aldosterone levels can also contribute to depression of baroreflex sensitivity, and they are associated with increased mortality in patients with severe heart failure. Experimental and clinical research should be further expanded to investigate the potential benefits of opposing the effects of aldosterone by use of specific antagonists or other potentially more potent pharmacological agents with favourable side-effect profiles.
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PMID:Aldosterone and heart failure. 868 70

In asymptomatic essential hypertensive patients with angiographically normal coronary arteries and without left ventricular hypertrophy, dipyridamole-induced ischemic-like ST segment depression may be a marker of coronary microvascular disease. In this study we evaluated, first, whether this cardiac abnormality is linked to structural or functional vascular abnormalities, and second, the effect of antihypertensive treatment by 12-month administration of the angiotensin converting enzyme (ACE) inhibitor captopril (50 mg twice a day orally). In essential hypertensives with dipypridamole echocardiography stress test (DET) (DET+, n = 8) and without (DET-, n = 8) ST segment depression greater than 0.1 mV during intravenous dipyridamole infusion (0.84 mg/kg over 10 min), we studied the forearm blood flow (FBF, venous plethysmography, mL/100) modifications induced by intrabrachial acetylcholine (Ach) (0.15, 0.45, 1.5, 4.5, 15 micrograms/100 mL/min x 5 min each), an endothelium-dependent vasodilator, and by sodium nitroprusside (SNP) (1, 2, 4 micrograms/100 mL/min x 5 min each), a smooth muscle cell relaxant compound. Minimal forearm vascular resistances (MFVR), an index of arteriolar structural changes, were also calculated. Both Ach and SNP caused greater vasodilation in DET- as compared to DET+ while MFVRs were lower in DET- compared to DET+. After treatment, both DET+ and DET- patients showed a significant and similar reduction in blood pressure and left ventricular mass index, while vasodilation to acetylcholine and sodium nitroprusside was increased only in the DET+ group. In addition, forearm minimal vascular resistances were significantly reduced only in DET+ patients, who showed disappearance of dipyridamole-induced ischemic-like ST segment depression. In conclusion, these data confirm that essential hypertensive patients with microvascular coronary disease are characterized by the presence of structural changes in the forearm vascular bed. Our results also indicate that both cardiac and forearm vascular abnormalities can be reversed by antihypertensive treatment with an ACE inhibitor.
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PMID:Presence of cardiovascular structural changes in essential hypertensive patients with coronary microvascular disease and effects of long-term treatment. 872 45

In our study the effects of angiotension converting enzyme inhibitor captopril and immunosuppressant agent d-penicillamine were investigated on inflammations mediated by kinins and on adjuvant arthritis in rat paw oedema tests. Kinins mediated inflammations were increased by small doses of captopril (0.04-5 mg/kg per os) in a dose dependent manner. However this effect of captopril was reduced at higher doses of the drug (5-400 mg/kg). In the case of d-penicillamine there was exerted an inflammation increasing effect similarly to captopril. Maximum value of this action could be measured at dose 100 mg/kg per os. After administration higher doses of d-penicillamine were not revealed any depression in inflammation increasing effect. In capillary resistance studies we have shown capillary resistance increasing action of captopril that was dose depend. However this effect was not found in the case of d-penicillamine. According to these finding kinins mediated inflammation increasing effects of captopril and d-penicillamine are suggested as a results of their ability inhibit angiotensin converting enzyme. Maximum depression at higher doses of captopril may be caused by its capillary resistance elevating action. In chronic inflammations studies we have shown developments of secondary symptoms of adjuvant arthritis inhibiting effects of captopril and d-penicillamine in a dose dependent manner. We assume that immunosuppressive action of both drug are responsible for reduction of chronic inflammations. Our study strengthens the argument that captopril can be used in therapy of rheumatoid arthritis. Further clinicopharmacological studies of captopril may clarify the role of this drug in therapy of rheumatoid diseases.
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PMID:[Effects pf captopril and D-penicillamine on kinins-mediated and chronic inflammation]. 908 38

The purpose of this study is to determine whether the administration of the ACE inhibitor cilazapril can lessen the adverse effects of ventricular remodeling, including systolic and diastolic dysfunction, modulation of fetal gene expression, increase of collagen genes, and depression of the sarcoplasmic reticulum (SR) Ca2+ ATPase gene in a myocardial infarcted (MI) rat model. At 1 day after MI, the animals were randomly assigned to cilazapril treatment or no treatment. We performed Doppler-echocardiographic examinations and measured cardiac mRNA in rats at 1 month and 3 months after MI (each group n = 8). The weights of the right (RV) and left ventricles (LV) in 1- and 3-month MI rats were significantly larger than those of the control rats. Cilazapril significantly prevented the increase. The MI rats showed systolic dysfunction, as evidenced by decreased fractional shortening (control, 34 +/- 3% vs. MI, 17 +/- 3%; P < 0.01) and ejection fraction measured by the modified Simpson's method (control, 61 +/- 2% vs. MI, 36 +/- 3%; P < 0.01) in rats at 1 month after operation. MI rats showed diastolic dysfunction, defined as increased peak early filling velocity, increased deceleration rate of the early filling wave, decreased late filling velocity, and an increase in the ratio of early filling to late filling velocity. Cilazapril significantly prevented systolic and diastolic dysfunction in rats after MI. The increases in beta-MHC, alpha-skeletal actin, ANP, and collagen I and III mRNAs in the nonischemic LV and RV were significantly suppressed by treatment with cilazapril. Depressed SR Ca(2+)-ATPase mRNA (nonischemic LV, 0.7-fold, P < 0.05 vs. control; RV, 0.5-fold, P < 0.05 vs. control) at 3 months after MI was significantly restored to normal levels by cilazapril. Cilazapril improved the adverse remodeling process by attenuating the progression of systolic and diastolic dysfunction, and prevented abnormal cardiac gene expression following MI.
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PMID:Effect of cilazapril on ventricular remodeling assessed by Doppler-echocardiographic assessment and cardiac gene expression. 960 33

The understanding of pharmacology of impotence has shown a steady improvement over the last 15 years which has resulted in a better appreciation of the neurovascular mechanisms of the erectile process especially at the level of the corpora cavernosa; however, central mechanisms which control libido and erection are not yet completely elucidated. Frequent diseases most commonly encountered in elderly patients--i.e. diabetes, hypertension, atherosclerosis, depression, etc--represent a frequent cause of erectile dysfunction (ED) and are treated with medications that can interfere with sexual functioning at the central and/or peripheral level. Antidepressants, including the tricyclics and the monoamine oxidase inhibitors, have been implicated in ED, decreased libido, and impaired ejaculation. Most antihypertensives have been associated with some erectile impairment, but diuretics seem to have little effect on erectile function. The calcium channel blockers and ACE inhibitors are associated with a low incidence of ED. Sympatholytic antihypertensives seldom cause importence but can cause retrograde ejaculation because of the relaxation of the smooth muscles in the prostatic urethra and bladder neck. The most commonly prescription drugs that can affect sexual function are briefly discussed and an integrated pharmacological approach to the patient with drug-induced ED is proposed.
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PMID:[Pharmacology of male sexual dysfunction]. 969 33

In view of the activation of renin-angiotensin system under conditions associated with pressure overload on the heart, we examined the effects of captopril, an angiotensin converting enzyme inhibitor, and losartan, an angiotensin II receptor antagonist, on cardiac function, myofibrillar ATPase and sarcoplasmic reticular (SR) Ca2+-pump (SERCA2) activities, as well as myosin and SERCA2 gene expression in hypertrophied hearts. Cardiac hypertrophy was induced in rats treated with or without captopril or losartan by banding the abdominal aorta for 8 weeks; sham operated animals served as control. Decrease in left ventricular developed pressure, +dP/dt and -dP/dt as well as increase in left ventricular end diastolic pressure and increased muscle mass due to pressure overload were prevented by captopril or losartan. Treatment of animals with captopril or losartan also attenuated the pressure overload-induced depression in myofibrillar Ca2+-stimulated ATPase, myosin ATPase, SR Ca2+-uptake and SR Ca2+-release activities. An increase in beta-myosin heavy chain mRNA and a decrease in alpha-myosin heavy chain mRNA as well as depressed SERCA2 protein and SERCA2 mRNA levels were prevented by captopril or losartan. These results suggest that both captopril and losartan improve myocardial function in cardiac hypertrophy by preventing changes in gene expression and subsequent subcellular remodeling due to pressure overload.
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PMID:Modification of cardiac subcellular remodeling due to pressure overload by captopril and losartan. 1005 50

Of the many publications on quality of life in medicine over the last 2 decades, only a minor fraction have been devoted to drug trials. The most frequently investigated are classes of drugs within cancer disorders, hypertension and depressive illness. Health-related quality-of-life (QOL) measurements are typically applied in chronic or subchronic disorders where the balance between effectiveness (disease-modifying drug effects) and safety (adverse drug reactions) are assessed by patients in terms of subjective well-being. In this context, quality of life is an attempt to help the doctor to listen to his or her patient. The components of QOL measurements are to be found within the PCASEE model where: P = physical indicators; C = cognitive indicators; A = affective indicators; S = social indicators; E = economic-social stressors or negative life events; and E = ego function or personality problems. Most variance in QOL measurements arises through operating in the cognitive (e.g. lack of control, concentration difficulties) or affective (e.g. depressed mood or anxiety) components. The most specific component is, of course, adverse drug reactions, which are typically gastrointestinal symptoms in cancer therapies, and circulatory symptoms and sexual function with antihypertensive drugs. However, the affective and cognitive components also have different weights within subclasses of drugs, such as antihypertensive agents. Thus, angiotensin converting enzyme inhibitors act on the affective component (depression and anxiety) and calcium channel blockers on the cognitive component (neurasthenia). In general, patients with cancer or hypertension give more reliable assessments of their cognitive and affective symptoms than their doctors do, while patients with primary depression are less reliable than their doctors or relatives in measuring changes in the affective components of their illness when they are ill. Health-related QOL measurements have not only an impact on the doctor-patient relationship but also involve a holistic approach to drug treatment, by checking all the PCASEE components.
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PMID:Quality-of-Life measurements for patients taking which drugs? The clinical PCASEE perspective. 1015 1

Our aim was to investigate the association of calcium channel blocker (CCB), beta-blocker, and ACE inhibitor medications with the risk of depression in diabetic patients. A case-control study was performed using an automated database (MediPlus, IMS) of 400 primary care practices in Germany including 972 diabetic cases with newly diagnosed depression in 1996 (index date) and 972 diabetic controls, matched for age, sex, and index date. The odds ratios (95%-confidence intervals) for depression, adjusted for type of practice, number of visits and prescriptions, hospitalization, cardiovascular diagnoses, and renal failure, were 2.2 (95% CI: 1.2-4.2) for exposure to CCB 6 months prior to index date, 2.6 (95% CI: 1.1-7.0) for beta-blockers, and 1.3 (95% CI: 0.8-2.2) for ACE inhibitors, respectively. Adjusted odds ratio for CCB (4.3; 95% CI: 1.7-13.5) and beta-blockers (4.5; 95% CI: 1.2-29.5) were higher with daily dosages above the median. Prescriptions of CCB and beta-blockers among diabetic patients may increase the risk of depression. Because this association may alternatively be explained by cardiovascular comorbidity, further studies will be necessary to investigate the link between these cardiovascular medications and depression.
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PMID:Cardiovascular drug prescriptions and risk of depression in diabetic patients. 1052 5

A 52 year old hypertensive Malay man, a smoker who presented with a one month history of mild chest discomfort not related to exertion and had a positive stress test with ST segment depression in the lateral leads. Coronary angiography showed stenosis in the right coronary artery and a coronary aneurysm in the proximal segment of his left anterior descending. The aneurysm was situated just distal to a stenotic lesion. The aneurysm is most likely related to atherosclerotic coronary artery disease. The patient was treated with oral nitrates, aspirin, angiotensin converting enzyme inhibitor and warfarin to prevent thromboembolism related to the coronary aneurysm. He remains asymptomatic one year after diagnosis.
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PMID:Solitary focal coronary artery aneurysm in a middle aged male with atypical chest pain. 1107 79


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