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

The spontaneously hypertensive rat (SHR) has been well established as a suitable model for studies of hypertension, but little is known about the processes of left ventricular (LV) hypertrophy and the changes in cardiac function in this model. The present study was designed to provide a noninvasive evaluation of the time-dependent alteration of cardiac function in male SHR at 4 to 24 weeks of age and age-matched Wistar-Kyoto rats (WKY). Echocardiographic studies were performed after blood pressure (BP) and heart rate (HR) were measured by a tail-cuff method. The body weight (BW) of SHR was lighter than that of WKY at all ages, and HR was consistently lower, with significantly elevated systolic BP from 4 weeks of age. In the echocardiographic study, LV mass at 4 weeks of age was similar between WKY and SHR, although the ratio of LV mass to BW was higher in SHR than WKY. The ejection fraction, fractional shortening (FS) and midwall FS did not differ between the two groups at 4 weeks, but after 8 weeks, these parameters were decreased in the SHR. The deceleration time was prolonged in SHR after 16 weeks and the E/A ratio was lowered at 12 weeks. We also analyzed the expression levels of calcineurin, which were found to be increased in both groups with age. These results suggest that calcineurin does not play a major role in the development of LV hypertrophy. Thus, in SHR, cardiac hypertrophy develops by 4 weeks of age, and systolic and diastolic dysfunction is evident at 2 to 3 months.
 ...
PMID:Noninvasive evaluation of the time course of change in cardiac function in spontaneously hypertensive rats by echocardiography. 1633 89

Sirolimus (SRL) is a new immunosuppressive drug approved for renal transplantation, but is being used increasingly in orthotopic liver transplantation (OLT). Compared with the calcineurin inhibitors, SRL has different mechanisms of action and side effects profile. Thus, this drug offers significant potential advantages over other immunosuppressive agents. SRL does not cause glucose intolerance, hypertension or renal failure, but it may cause dyslipidemia, hepatic artery thrombosis, thrombocytopenia, anemia, leukopenia, oral mucosa ulcers, edema, arthralgias and wound complications. SRL inhibits the signal of interleukin 2 at a post-receptor level, inhibiting lymphocyte proliferation and fibroblast proliferation. It also has antineoplastic and antifungal effects. We report a 10 years old girl who underwent OLT, experiencing a biopsy-proven recurrent acute rejection (AR) in spite of using three immunosuppressive agents (tacrolimus, mofetil micofenolate and steroids). She developed diabetes mellitus as a consequence of the immunosuppressive therapy. She was rescued with SRL, not experiencing AR again. Mofetil micofenolate, steroids and insulin could be discontinued and tacrolimus doses were reduced, without experiencing severe complications. SRL is a new and safe immunosuppressive agent for rescue in patients with OLT and recurrent AR.
 ...
PMID:[Sirolimus for rescue of recurrent acute rejection and diabetes mellitus after liver transplantation: report of one case]. 1634 73

Endothelial dysfunction and damage are systemic processes that are recognised to play a central role in the pathogenesis of hypertension and atherosclerotic cardiovascular disease. Renal failure is associated with impaired endothelium dependent vasodilatation that is partly a consequence of increased circulating levels of asymmetric dimethyl arginine. Endothelial dysfunction persists, although it is improved, after renal transplantation. Statins appear to improve endothelial dysfunction, as does withdrawal of calcineurin inhibitors, although there is no evidence that these strategies improve patient or graft survival. The situation in transplant recipients is complicated by the fact that endothelial dysfunction (within the graft vasculature) may be a separate process contributing to chronic allograft nephropathy and to circulating levels of endothelial cells and their components, thus limiting the utility of circulating markers of endothelial damage in this population.
 ...
PMID:Endothelial dysfunction in renal transplant recipients. 1638 45

The calcineurin inhibitors (CNIs) cyclosporine and tacrolimus are routinely used for immunosuppression following heart transplantation in conjunction with an antiproliferative agent with or without maintenance steroids. In randomized multicenter trials both agents showed similar efficacies to prevent rejection and death within the first year after transplant. Neither cyclosporine nor tacrolimus have been shown to prevent coronary allograft vasculopathy. Their use is limited by many side effects like kidney damage, hypertension, new-onset diabetes, and hyperlipidemia, although they may have different cardiovascular side effect profiles. The choice of CNIs seems to be currently dictated by their adverse effect profiles, by the results obtained for the individual patient, and possibly by institutional preference.
 ...
PMID:Calcineurin inhibitors in heart transplantation. 1638 14

Cells have the capability of defending themselves from various stressors by activating a genetic program with the production of substances known as heat shock proteins (Hsps) and their regulatory partners, the heat shock transcription factors. Hsps play a major role in systemic hypertension, coronary artery disease, carotid atherosclerosis, myocardial infarction and myocardial ischemia. In this review we discuss the interaction between Hsp70 and CaN which was carried out in our laboratory. We demonstrated that the cardiac Hsp70 stimulated a 2-fold increase in calcineurin (CaN) activity. In addition, the pull-down assay revealed that Hsp70 directly interacts with CaN. Furthermore, expressed cardiac specific Hsp70 was phosphorylated in vitro by cAMP-dependent protein kinase. The phosphorylated Hsp70 was unable to activate the phosphatase activity of CaN. For the first time we demonstrated that Hsp70 is phosphorylated by cAMP-dependent protein kinase and provides an on/off switch for the regulation of CaN signaling by Hsp70. This will lead to therapeutic benefit in human diseases such as atherosclerosis, cardiomyopathy, congestive heart failure, and ischemia.
 ...
PMID:Interaction between heat shock protein 70 kDa and calcineurin in cardiovascular systems (Review). 1646 87

The relationship between the kidney and blood pressure control is complex. Monogenetic forms of hypertension have recently been identified that implicate specific mutations responsible for blood pressure control. The thiazide sensitive Na-Cl cotransporter (NCC) has been implicated in the control of blood pressure, however a direct link between the kidney NCC and blood pressure regulation is lacking. Here, we report a case of chimerism in which a kidney from a patient with Gitelman syndrome was transplanted into a non-Gitelman hypertensive recipient. After transplantation, postural hypotension resulted, necessitating discontinuation of all antihypertensive medications used for treatment of calcineurin-induced hypertension. This is the first reported case of acquired Gitelman syndrome after transplantation. Transplantation of a Gitelman "kidney" into a hypertensive recipient provides additional support for the role of the kidney NCC in blood pressure regulation. Furthermore, this case suggests the potential use of thiazide diuretics in the treatment of calcineurin-induced hypertension.
 ...
PMID:Correction of renal hypertension after kidney transplantation from a donor with Gitelman syndrome. 1647 87

Adverse effects associated with calcineurin inhibitors may impact their clinical utility in some patients. This study characterizes the clinical outcomes of liver transplanted (LT) patients who experienced diabetes mellitus (DM) on tacrolimus-based regimen and were converted to cyclosporine-based therapy. Since January 2002, all patients with DM on a tacrolimus-based regimen were recruited and converted to cyclosporine-based therapy, after a 6-month minimal follow-up after LT. Clinical and laboratory data related to the clinical course of the patients were recorded. Twenty-five patients were included after a median delay of 54 months after LT [seven women and 18 men, 51 years (range 30-69)]. There were 11 patients with insulin-treated DM (ITDM), 14 patients with noninsulin-treated DM (NITDM), and the glycemic control was poor (HbA1c > 6.5%) in 13/25 patients (52%). After a median follow-up of 20 months after conversion, there were four patients with ITDM, 17 patients with NITDM, and four patients without DM, and the glycemic control was poor in 3/25 patients (12%). Four patients returned to tacrolimus because of arterial hypertension or digestive side-effects. In conclusion, our results suggest that conversion from tacrolimus to cyclosporine in stable LT patients with DM is well tolerated and beneficial on glycemic control.
 ...
PMID:Conversion from tacrolimus to cyclosporine in liver transplanted patients with diabetes mellitus. 1649 79

For many years, calcineurin has been a familiar molecule as a target of the immunosuppressive agents cyclosporin A and FK-506. Calcineurin inhibition interferes with T cell signaling by preventing activation of the transcription factor NFATc. However, calcineurin is expressed in most tissues in the body, and calcineurin inhibition undoubtedly alters many other cellular processes. As a result, serious side effects of calcineurin inhibitors regularly occur, including hypertension and renal dysfunction. Because nephrotoxicity is often a barrier to continued clinical use of calcineurin inhibitors, understanding the role of calcineurin in the kidney is of particular importance. Recent work has demonstrated that the two main isoforms of the catalytic subunit of calcineurin, Aalpha and Abeta, may have distinct functions, particularly in the kidney. Calcineurin isoforms may be differentially expressed, and/or the activity of each may be differentially regulated, leading to tissue-specific functions. Differences between the action of the two isoforms are most evident in knockout mice lacking each isoform. Mice lacking the beta-isoform are characterized principally by altered development and function of immune cells. alpha-Knockout mice, in contrast, can still be immune suppressed by cyclosporin A but display pervasive developmental defects, including renal dysfunction. Therefore, it is intriguing to consider that while the beta-isoform may be responsible for calcineurin action in T cells, the alpha-isoform may be the predominant catalytic isoform in the kidney. This conclusion, if correct, may have substantial clinical implication for novel strategies to selectively target calcineurin action in T cells without associated nephrotoxicity.
 ...
PMID:An emerging role for calcineurin Aalpha in the development and function of the kidney. 1652 22

The mTOR inhibitor sirolimus improves renal transplant function compared with the nephrotoxic calcineurin inhibitors. We evaluated retrospectively the adverse events in 119 of 134 patients getting sirolimus which seemed to be caused by sirolimus. Patients were converted to sirolimus because of malignancies (n = 47), a creeping creatinine (n = 33), or hypertension (n = 26). One cohort had started sirolimus from the time of transplantation (n = 28). A rise in serum lipids and a decrease in hemoglobin were seen relatively regularly, while arthralgia, peripheral edema, gastrointestinal complaints, skin disorders, electrolyte disturbances, and infections occurred only occasionally. Interestingly, 31% of patients developed doubling or more proteinuria. Among renal biopsies, 9/13 showed a glomerulopathy which in 6 cases was de novo and in 3 cases, a presumed recurrence of the primary kidney disease. Thus, we think that caution is required, particularly in connection with preexisting glomerular disease.
 ...
PMID:Side effects of sirolimus. 1664 52

Cardiac allograft vasculopathy (CAV), is characterized by heterogeneous proliferative thickening of the vascular intima of the cardiac allograft vasculature. Since its presentation is commonly clinically silent, early diagnosis and preventative therapy are critical. Preventative therapy including optimization of immunosuppressive therapy and treatment of comorbidities associated with CAV progression must be initiated early since most of the intimal thickening occurs during the first year posttransplant. Long-term use of calcineurin inhibitors is associated with a high incidence of chronic renal disease and also contributes to hyperlipidemia and hypertension, all of which may exacerbate CAV. In addition, statins, antihypertensive agents and anti-CMV agents all have demonstrated benefits in reducing CAV. Once established, the limited treatment options include nonpharmacologic interventions such as retransplantation, percutaneous coronary interventions, coronary artery bypass grafting, transmyocardial laser revascularization and heparin-induced/mediated extracorporeal LDL plasmapheresis (HELP). As the use of new assessment tools increases our understanding of this disease, better preventative and treatment strategies are evolving.
 ...
PMID:Contemporary concepts in prevention and treatment of cardiac allograft vasculopathy. 1668 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>