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)

Cyclosporine is a fungal metabolite increasingly used as an immunosuppressive agent in organ transplantation. It provides immunosuppression primarily through reversible inhibition of T-lymphocytes, without myelotoxicity. Cyclosporine appears to inhibit primary activation of helper cells and to decrease the production of lymphokines by these cells. Cyclosporine becomes widely distributed into tissue compartments and is metabolized primarily by the liver. Serum trough levels, measured by radioimmunoassay or high pressure liquid chromatography, are commonly monitored and sometimes used for dose adjustments. Cyclosporine has been used in human renal, cardiac, liver, bone marrow, and pancreatic transplantation, as well as in other experimental animal models. It has a narrow therapeutic index, with major complications arising from nephrotoxicity, hypertension, and hepatotoxicity. Cyclosporine also has some antischistosomal and antimalarial activity.
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PMID:Cyclosporine. 241 10

Cyclosporine is a potent immunosuppressive agent with no appreciable effect on the bone marrow and a selective inhibitory effect on helper T cells. Oral cyclosporine was first used to prevent organ rejection but also has been reported to be effective in other disorders. In cutaneous diseases that respond to oral cyclosporine helper T cells appear to be involved in their pathogenesis. This article reviews the cutaneous diseases that have been treated with cyclosporine and its pharmacology and side effects. Two significant adverse side effects are renal dysfunction and hypertension, both of which are reversible when short-term low-dose (less than 5 mg/kg per day) oral cyclosporine is discontinued. Lymphoma is unlikely in an otherwise healthy patient who has received low-dose oral cyclosporine for limited periods. The use of oral cyclosporine in any patient should be carefully considered in terms of the risk/benefit ratio and needs to be carried out under close medical supervision. In view of the limited experience with cyclosporine in dermatology, whenever possible its use should be confined to formal clinical studies with established protocols and guidelines. Further controlled studies need to be performed to evaluate the efficacy of low-dose cyclosporine in many dermatoses and its side-effect profile, particularly over the long term.
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PMID:Cyclosporine in dermatology. 227 33

With the aim to improve renal graft function and to prevent hypertension, we used the calcium-antagonist diltiazem in a prospective randomized study in 30 consecutive cadaveric renal transplanted patients from september 1987 to may 1988. The diltiazem (D+) group comprised 14 patients receiving a loading dose of 0.3 mg/kg followed by a 2 micrograms/kg/d continuous IV infusion of D started as soon as possible after clamp on renal artery removal. D was then given orally (120-180 mg/d) throughout the study. 16 patients without D composed the D- group. Cyclosporine A (csa) was started either just before transplantation (15 mg/kg/d orally) in 18 patients (9 D+ and 9 D-) or after 2-3 weeks of poly or monoclonal antibodies (5 D+ and 7 D- at 10 mg/kg/d. In addition to the usual monitoring, inulin (for GFR) and PAH (for ERBF), clearances were performed 7 days and 3 months after transplantation. If hypertension (blood pressure greater than 160/90 mm Hg) occurred, all but calcium-antagonists antihypertensive agents were used in both groups. Between D+ and D-, the number of patients requiring haemodialysis during the first week was not different (7/14 vs 5/16) like the number of dialysis session per patient (1.4 vs 1.1) day 7 GFR (19 +/- 22 vs 23 +/- 20) and day 7 ERBF (146 +/- 147 vs 226 +/- 224) ml/mn/1.73 m2; at 3 months 13/14 (93 p. 100) vs 12/15 (80 p. 100) of the grafts are functioning (NS), GFR (34 +/- 17 vs 33 +/- 10) and ERBF (242 +/- 90 vs 236 +/- 117) are not different.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of diltiazem on arterial pressure and renal function in renal transplanted and cyclosporin A treated subjects. Results after 3 months of a prospective study]. 251 Jun 52

Arterial hypertension is a common side effect of cyclosporine A therapy; however, the cellular mechanism of cyclosporine A-induced hypertension is still unknown. The present study, therefore, examined the effect of cyclosporine A on Ca2+ kinetics and contraction in primary cultures of vascular smooth muscle cells. Cyclosporine A (10 micrograms/ml) did not affect resting intracellular free Ca2+ ([Ca2+]i) levels (151 +/- 10 vs. 146 +/- 5 nM, NS), but augmented the 10(-8) M arginine vasopressin-induced increase of [Ca2+]i (delta 76 +/- 4 vs. delta 172 +/- 6 nM, p less than 0.001). This effect of cyclosporine A was also observed in Ca2+-free medium. Arginine vasopressin-stimulated [Ca2+]i efflux within 30 seconds compared with baseline efflux rates (1,644 +/- 146 vs. 2,591 +/- 373 cpm/mg prot/30 sec, p less than 0.005), but this transient effect was significantly greater (p less than 0.001) with arginine vasopressin plus cyclosporine A (1,702 +/- 133 vs. 5,605 +/- 1235 cpm/mg prot/30 sec, p less than 0.01). Basal 45Ca2+ efflux rates were not affected by cyclosporine A, and prior incubation of the cells with cyclosporine A was required to elicit the augmentory effect. 45Ca2+ uptake was measured to examine the mechanism by which cyclosporine A may affect [Ca2+]i stores. Cyclosporine A increased Ca2+ uptake when compared with control (6.38 +/- 0.69 vs. 10.99 +/- 0.59 x 10(3) cpm/mg prot/5 min, p less than 0.001). This effect was not blocked by the Ca2+ antagonist verapamil. Arginine vasopressin (10(-8) M) induced contraction of smooth muscle cells with 25.5% of the cells responding.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1989 Apr
PMID:Potential mechanism of cyclosporine A-induced vascular smooth muscle contraction. 253 92

Nine patients with chronic posterior endogenous uveitis of varying aetiology, not satisfactorily controlled with systemic corticosteroids alone, were treated with low dose oral Cyclosporin A (mean maintenance dose 4.0 +/- 1.1 mg/kg/day). Six of the nine patients also continued to receive oral prednisolone (15 mg/day or less). During a follow up period of 6-30 (mean 17) months, seven have shown sustained visual improvement. Nephrotoxicity was the major side effect with serum creatinine concentration (mean +/- 1SD) rising from 91 +/- 7 mumol/l to 115 +/- 13 mumol/l (0.01 less than p less than 0.05) after the first twelve months of treatment. Other observed side effects have included taste disturbance, hypomagnesaemia, and hypertension. Cyclosporin A treatment is of value in the management of severe intraocular inflammation, unresponsive to conventional therapy, but the optimum duration of therapy remains to be established and nephrotoxicity is the major dose limiting effect.
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PMID:Low dose cyclosporin A therapy in chronic posterior uveitis. 261 72

The present study was undertaken to study the mechanism of cyclosporine-induced nephrotoxicity and hypertension. Cultured rat microvascular endothelial cells were exposed to cyclosporine for up to six days at one of the following concentrations: 10, 50, 250, and 1000 ng/ml of culture medium. Cyclosporine inhibited endothelial cell replication in a dose-dependent manner; at higher concentrations (250 and 1000 ng/ml), cell replication decreased by as much as 70 to 90% of controls at four and six days post-treatment, with no evidence of increased cell death. Drug-treated endothelial cells revealed abnormal morphological changes such as formation of cytoplasmic vesicles and nucleolar changes. Prostacyclin release by endothelial cells was increased by about threefold with the addition of cyclosporine (P less than 0.01). Indomethacin significantly decreased prostacyclin release by endothelial cells in the presence or absence of cyclosporine (P less than 0.01). Our data suggest that cyclosporine-induced nephrotoxicity may be mediated, at least partly, by the inhibitory influence of cyclosporine on the regenerative response of microvascular endothelial cells to injury, and the resultant alterations in prostacyclin production by these cells.
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PMID:Cyclosporine toxicity on cultured rat microvascular endothelial cells. 265 56

We retrospectively reviewed the long-term results in 46 patients who survived at least 1 year after liver transplantation. Only one death has occurred, and one patient has required retransplantation. Biochemical liver function tests showed median values in the normal range, except for mild elevation of serum gamma-glutamyltransferase. In patients with primary biliary cirrhosis, these test results were completely normal. A liver biopsy 1 year after transplantation disclosed normal histologic findings in 31 patients (67%). The other patients had either transient (acute rejection) or stable (chronic rejection) abnormalities, except for two patients with progressive graft dysfunction attributable to chronic rejection. A clinically significant vascular anastomotic abnormality was noted in one patient who had hepatic artery thrombosis. Late bile duct complications occurred in 15% of patients, all of whom had a satisfactory outcome after surgical or radiologic intervention. Cyclosporine-related nephrotoxicity and hypertension each occurred in 67% of patients; however, conversion to a low-dose cyclosporine-azathioprine regimen yielded stabilization of renal function after the first postoperative year, and hypertension has been easily controlled medically. Diabetes necessitating insulin treatment developed in three patients. The body weight of the study patients had increased by a median of 6.5 kg at 1 year but stabilized thereafter. Subjective well-being and satisfaction with life were reported by 91% of the patients. Of the 46 patients, 26 were employed, 16 were homemakers, and only 4 did not work, 2 because of transplant-related medical problems. Thus, we conclude that liver transplantation rehabilitates patients with end-stage liver disease and enhances their quality of life.
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PMID:Beyond 1 year after liver transplantation. 265 1

Heart transplantation is becoming an accepted treatment for children with irreversible and profoundly disabling cardiomyopathy. The risk is much higher when there is underlying congenital heart disease, and even moderately elevated pulmonary vascular resistance is a contraindication to orthotopic heart transplantation. Heterotopic or heart-lung transplantation may be considered in patients with elevated pulmonary vascular resistance. In a few centers, heart transplantation is being performed as an alternative to palliative surgical procedures in children with hypoplastic left heart syndrome. Chronic immune suppression is necessary in all patients postoperatively. Cyclosporine and prednisone are the mainstays of therapy, and azathioprine is often added to the regimen. ATG is used prophylactically in the immediate postoperative period and acute rejection episodes are treated with pulses of prednisone, ATG, or OKT3. Infection continues to be a major problem, and the chronic long-term effects of both rejection and the drugs used to treat it, especially cyclosporine, are also very important. Coronary artery disease and lymphoproliferative disease are causes of death, and hypertension and decreased renal function are present in almost all survivors. The shortage of donor hearts is becoming a progressively more important problem and may affect selection criteria in the future. On the positive side, most children can return to age-appropriate activities following transplantation and they seem to tolerate their chronic illness and its attendant repeated invasive procedures surprisingly well.
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PMID:Cardiac transplantation in children. 265 82

Cyclosporine-treated renal allograft recipients frequently suffer CsA-related nephrotoxicity and hypertension. This study demonstrates that glomerular filtration rate is reduced acutely by 13% (P less than 0.02) and renal vascular resistance increased by 30% (P less than 0.05), immediately after patients take their CsA dose. The reduction in GFR is directly related to their trough CsA level (r = 0.82; P less than 0.01). The lower the trough CsA level the greater the fall in GFR after the CsA dose. Plasma renin activity does not increase after the CsA dose (pre-CsA 0.6 +/- 0.2 ng/L/sec vs. post-CsA 0.4 +/- 0.1 ng/L/sec; P = NS), and therefore cannot be responsible for the reduction in renal function. Short-term nifedipine treatment is effective in preventing the acute reduction in GFR (P less than 0.05). This occurred despite no apparent effect of nifedipine in altering trough or post-dose CsA levels. Furthermore nifedipine was effective in lowering both the mean arterial blood pressure (109 mmHg to 94 mmHg; P less than 0.01) and the elevated renal vascular resistance (25% reduction; P less than 0.02) observed in these patients. These results suggest that nifedipine may be a suitable agent for limiting acute CsA nephrotoxicity and for treating CsA-associated hypertension in renal allograft recipients.
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PMID:Cyclosporine-induced renal dysfunction in human renal allograft recipients. 268 8

The effects of cyclosporine on the functional characteristics of human subcutaneous resistance vessels were investigated. Resistance vessels were obtained from normal subjects undergoing routine surgery. Incubation with cyclosporine did not alter the resting tone of the vessels, but decreased the maximum contractile response and the sensitivity of the vessels to stimulation with exogenous noradrenaline and potassium. Cyclosporine decreased the rate of spontaneous relaxation and inhibited endothelium-dependent relaxation as assessed by the response to acetylcholine. Paradoxically, endothelium-independent relaxation as assessed by the response to sodium nitroprusside was augmented. Hypertension induced by cyclosporine may, in part, be explained by a reduction in relaxation of peripheral resistance vessels.
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PMID:Cyclosporine A inhibits relaxation but does not induce vasoconstriction in human subcutaneous resistance vessels. 270 8


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