Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All-trans retinoic acid (atRA) is a biologically active metabolite of vitamin A that plays an important role in cell differentiation and proliferation. Although neointimal formation after balloon injury of rat carotid artery is inhibited by atRA, the mechanisms are not clearly understood. Because the renin-angiotensin system is one of the crucial components of atherosclerosis, we examined the effects of atRA on the expression of angiotensin II type 1 receptor (AT(1)-R) in vascular smooth muscle cells. atRA (1 micromol/L) decreased the AT(1)-R mRNA level by 50% after 24 hours; AT(1)-R number was also reduced to the same extent after 48 hours. atRA markedly suppressed promoter activity of the AT(1)-R promoter-luciferase construct, but AT(1)-R mRNA stability was not affected. Cycloheximide blocked the atRA-induced decrease in AT(1)-R mRNA expression, suggesting that this process requires de novo protein synthesis. Simultaneous treatment with an agonist (Ro40-6055) specific for retinoic acid receptor (RAR) and an agonist (Ro25-7836) specific for retinoid X receptor (RXR) suppressed the AT(1)-R mRNA expression comparable to that with treatment with atRA, suggesting that the RAR/RXR heterodimer mediates the effect of atRA in AT(1)-R downregulation. These results suggest that atRA suppressed AT(1)-R mRNA transcription through new protein synthesis induced by RAR/RXR-dependent transcription. This study provides novel insight into a role of atRA as an important molecule that regulates AT(1)-R gene expression and provides possible mechanisms for the suppression of neointimal formation by atRA.
Hypertension 2000 Jan
PMID:Downregulation of angiotensin II type 1 receptor by all-trans retinoic acid in vascular smooth muscle cells. 1064 14

Noncardiogenic pulmonary edema (NCPE) is a rare and less well-recognizable pulmonotoxic syndrome of anticancer therapy than pneumonitis/fibrosis. NCPE is a clinical syndrome characterized by simultaneous presence of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph, and no evidence of left atrial hypertension/congestive heart failure. The diagnosis of drug-related NCPE relies upon documented exclusion of any infectious, metabolic, or cancer-related causes. The time proximity to therapy with drugs that are known to precipitate NCPE, any preceding episodes of flu-like symptoms during previous chemotherapy courses and possible response to corticosteroids may further support such a diagnosis. Cancer therapeutic agents clearly associated with NCPE are cytarabine, gemcitabine, and interleukin-2, as well as all-trans retinoic acid in acute promyelocytic leukemia patients, while a few other compounds have rarely or occasionally been implicated. The pathophysiology of lung injury in drug-induced NCPE remains unclear. There are indications suggesting that both a direct cytotoxic insult to the lung epithelial cells and induction of a cytokine-triggered inflammatory response may be involved in its pathogenesis. By distinction to drug-induced pulmonary pneumonitis that may lead to permanent pulmonary fibrosis, NCPE if not fatal, can be reversed upon prompt recognition, following immediate discontinuation of the offensive drug and start of intensive supportive treatment and intravenous corticosteroids.
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PMID:Noncardiogenic pulmonary edema: an unusual and serious complication of anticancer therapy. 1130 27

Sixty-three cases with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). The rates of hyperleukocytosis, intracranial hypertension, retinoic acid syndrome were 57.1%, 9.5%, and 3.2% respectively. Mortality of the treatment was 11.1%. Under ATRA treatment, hyperleukocytosis leading to leukostasis was the cause of death in patients with APL. We therefore suggest that the patients with such leukocyte levels (that is, 5.0 x 10(9).L-1 on the 6th day, 10.0 x 10(9).L-1 on the 10th day, 15.0 x 10(9).L-1 on the 15th day) can be used as guidelines for starting chemotherapy(homoharringtonine); before ATRA treatment, while leukocyte counts are > 10 x 10(9).L-1, the patients only receive homoharringtonine; when leukocyte counts are < or = 5.0 x 10(9).L-1, the patients receive a combination of homoharringtonine and ATRA. Retinoic acid syndrome is a distinctive complication of ATRA therapy in the patients with APL. While the syndrome occurs, the treatment of ATRA must be stopped and corticosteroids must be used.
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PMID:[Severe side effects of the treatment of acute promyelocytic leukemia with all-trans retinoic acid]. 1221 69

There are in vitro data linking all-trans retinoic acid (atRA) with inhibition of hypertrophy and hyperplasia in cardiomyocytes, vascular smooth muscle cells, and fibroblasts. In the present study, we tested the hypothesis that chronic treatment with atRA may blunt the process of myocardial remodeling in spontaneously hypertensive rats (SHR). Four-week-old male SHR were treated with atRA (5 or 10 mg.kg-1.day-1) given daily for 3 mo by gavage; age- and sex-matched Wistar-Kyoto rats (WKY) and placebo-treated SHR served as controls. At the end of the treatment period, cardiac geometry and function were assessed by Doppler echocardiography. Histological examination and RIA were performed to evaluate medial thickening of intramyocardial and renal arteries, perivascular and interstitial collagen content, and atrial natriuretic peptide (ANP) and IGF-I in the heart, respectively. The novel finding of the present study is that atRA prevented hypertrophy of intramyocardial and intrarenal arteries and ventricular fibrosis. However, atRA treatment did not lower blood pressure or left ventricular weight and left ventricular weight-to-body weight ratio in SHR. atRA did not change cardiac geometry and function as assessed by Doppler echocardiography. atRA showed no influence on either ANP or IGF-I levels. In conclusion, the present study suggests that chronic atRA treatment prevents medial thickening of intramyocardial and intrarenal arteries and ventricular fibrosis during the development of hypertension. Left ventricular hypertrophy and cardiac geometry and function are not changed by atRA treatment.
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PMID:Chronic all-trans retinoic acid treatment prevents medial thickening of intramyocardial and intrarenal arteries in spontaneously hypertensive rats. 1277 63

We report a case of benign intracranial hypertension (BIH) caused by all-trans retinoic acid (ATRA) in a patient with acute promyelocytic leukemia. A 21-year-old male was admitted to our hospital with pancytopenia. He was diagnosed as having acute promyelocytic leukemia due to increased promyelocytes, and PML-RAR alpha chimeric mRNA was detected. The administration of ATRA and idarubicin was started immediately. After 26 days of the chemotherapy, he complained of diplopia. Ophthalmologic examination revealed bilateral papilledema and hemorrhage. The cerebrospinal fluid showed an increase in pressure, but no other abnormalities. Computed tomography showed no intracranial abnormalities. The orbital MR imaging showed distension of the perioptic subarachnoid space and flattening of the posterior sclera. A diagnosis of BIH was made. After the discontinuation of ATRA, the symptoms improved and the MR abnormalities disappeared. As far as we know, there have been no reports illustrating MR abnormalities of BIH caused by ATRA, for the diagnosis and monitoring of which orbital MR imaging can provide important clues.
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PMID:[MR imaging provides important clues for the diagnosis of benign intracranial hypertension by all-trans retinoic acid in a patient with acute promyelocytic leukemia]. 1504 22

There is increasing evidence that all-trans retinoic acid (atRA) influences gene expression of components of renin-angiotensin system (RAS), which plays a pivotal role in the pathophysiology of essential hypertension. To further validate effects of atRA on the RAS and to assess the possibility that atRA affects the activity of angiotensin-converting enzyme 2 (ACE2), gene, and protein expression of ACE2 have been examined by real-time polymerase chain reaction and Western blot methods in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats were treated with atRA (10 or 20 mg x kg(-1) x day(-1)) or placebo given as daily intraperitoneal injection for 1 month. ACE2 expression was markedly decreased in placebo-treated SHR when compared with WKY rats. However, in atRA-treated SHR, a significant upregulation of ACE2 expression was observed in heart and kidney. In conclusion, chronic atRA treatment increases gene and protein expressions of ACE2, resulting in the reduction of blood pressure and the attenuation of myocardial damage in SHR, which suggests that atRA may be an attractive candidate for the potential prevention and treatment of human essential hypertension.
Hypertension 2004 Dec
PMID:Upregulation of angiotensin-converting enzyme 2 by all-trans retinoic acid in spontaneously hypertensive rats. 1547 83

Renin, as a component of the renin-angiotensin system, plays important roles in the regulation of blood pressure, electrolyte homeostasis, and mammalian renal development. Transcription of renin genes is subject to complex developmental and tissue-specific regulation. Progress has been made recently in elucidating the molecular mechanisms involved in renin gene expression. Using mouse As4.1 cells, which have many features characteristic of the renin-expressing juxtaglomerular cells of kidney, a proximal promoter region (-197 to -50 bp) and an enhancer (-2866 to -2625 bp) have been identified in the mouse renin gene, Ren-1(c), that are critical for its expression. The proximal promoter region contains at least 7 transcription factor-binding sites, including a binding site for the products of Hox, developmental control genes. The enhancer consists of at least 11 transcription factor-binding sites and is responsive to various signal transduction pathways, including cAMP, retinoic acid, endothelin-1, and cytokines, to alter renin mRNA levels. Sequence highly homologous to the mouse enhancer is also found in the human and rat renin genes. How these regulatory regions function in vivo will be the focus of future study.
Hypertension 2005 Jan
PMID:Transcriptional regulation of renin: an update. 1554 7

Bone marrow transplant nephropathy (BMTN) classically presents more than 100 days after transplantation as an acute nephritis with hypertension, azotaemia and anemia that usually results in end stage renal failure (ESRF). The risk of developing BMTN may be greater with the use of more intensive chemotherapy and higher total body and tumor bed irradiation. Cis-retinoic acid (RA) may further increase the risk of developing BMTN. Here, we report the cases of two children who developed typical clinical and biochemical features of BMTN. They were both treated for stage IV neuroblastoma with chemotherapy, bone marrow transplant (BMT) conditioning that included total body irradiation and RA therapy after BMT, although the patient in case 1 had established renal insufficiency prior to the commencement of RA. Renal biopsy of these children showed classical BMTN histology, and the renal manifestations progressed quickly; the patient in case 1 became dialysis dependent by 1 year post-bone marrow transplant. Recently, RA has been added to the post-BMT therapy in children with stage IV neuroblastoma. The occurrence of BMTN in two children treated with RA in our unit is unlikely to be coincidental. Although RA has been shown to confer a significant survival advantage in this disease, animal studies and a previous case report have suggested it could increase the toxic effects of chemotherapy and renal irradiation. It is likely that RA contributed to the deterioration in renal function in these patients.
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PMID:Retinoic acid may increase the risk of bone marrow transplant nephropathy. 1571 54

Isolated abducens nerve palsy is a rare complication of treatment with various drugs. Here, the authors report the case of a 23-year-old female with isolated left abducens nerve palsy after long-term retinoic acid therapy. The association is based on the temporal relationship and the exclusion of other possible etiologic factors following extensive laboratory and imaging diagnostics. The authors suggest that isolated abducens nerve palsy may be a presenting sign of a toxic neuropathy associated with retinoic acid therapy. After the exclusion of other organic lesions, especially idiopathic intracranial hypertension, and an assessment of the risk-benefit ratio, discontinuation of treatment must be considered in such cases.
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PMID:Isolated abducens nerve palsy associated with retinoic acid therapy: a case report. 1625 Nov 42

Isotretinoin (13-cis-retinoic acid) is a retinoid that is used to treat cystic acne, comedonal acne, and other diseases. For the treatment of acne, isotretinoin is dosed at 0.5 to 2 mg/kg daily for 5 months with a target total dose of approximately 120 mg/kg. Its most common side effects are mucocutaneous and ocular in nature (ie, cheilitis, ocular sicca, and decreased dark adaptation). It can also cause xerosis. Patients should be made aware of these side effects before taking isotretinoin and also that utilization of moisturizers and eye drops can help to mitigate such side effects. Sometimes, however, the dose of isotretinoin needs to be decreased to reduce the induction of side effects. Isotretinoin's most significant side effect is the induction of birth defects if a fetus is exposed to isotretinoin, which is pregnancy category X. Isotretinoin should be used with 2 forms of birth control by fecund women. It can rarely increase serum levels of triglycerides, which can, if very elevated, be related to the development of pancreatitis and xanthomas. Isotretinoin's well-documented but rarer side effects include intracranial hypertension. It can induce bony changes. A review of the literature demonstrates that isotretinoin is not linked to depression and suicide. Facial swelling has been linked to isotretinoin use in 3 previous case reports. We note herein the first case of facial swelling that occurred in an acne patient being treated with isotretinoin who at the time the swelling developed had no cysts, comedones, pustules, or evidence of bacterial infection. Possible reasons for the patient's facial swelling include some type of retinoid induced angioedema, exacerbation of inflammation by isotretinoin, and isotretinoin induced capillary leak syndrome.
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PMID:Facial edema induced by isotretinoin use: a case and a review of the side effects of isotretinoin. 1670 87


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