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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2000-9-27
pubmed:abstractText
The cardiovascular and renal pathophysiology associated with chronic renal allograft rejection under triple drug immunosuppressive treatment was studied using a recently developed model (Brown Norway (BN) rats) in a 6-week experiment. Renal transplantation was performed to 10-week-old rats in a rat strain combination of Dark Agouti (DA) --> BN. The right kidney was removed from another group of BN rats (uninephrectomized). A triple drug treatment comprising cyclosporine (10 mg/kg subcutaneously, s.c.), azathioprine (2 mg/kg s.c.) and methylprednisolone (1.6 mg/kg s.c.) was given to each rat daily for 6 weeks. A control group underwent no operations nor drug treatment. After the transplantation, the systolic blood pressure in this group was increased from 116 +/- 2 to 166 +/- 2 mmHg, while in the uninephrectomized group the rise was from 115 +/- 4 to 146 +/- 4 mmHg, and no change was observed in the blood pressures of the control group. The vascular relaxation responses of mesenteric arterial rings in vitro to acetylcholine were inhibited in both the transplantation group and the uninephrectomized group as compared with the control group, but few significant differences were found in the contraction responses to noradrenaline and potassium chloride. Graft histology was examined after 6 weeks, quantified by using the chronic allograft damage index (CADI). Changes specific to a chronic rejection reaction were observed in the allografts (CADI mean 6.0) but no injuries were seen in the rats' own kidneys (CADI mean 1.2). Our findings show that allograft rejection in BN rats after renal transplantation is associated with the development of arterial hypertension. The combination of cyclosporine, methylprednisolone and azathioprine also rises blood pressure in uninephrectomized BN rats. The hypertensive effects of the drug treatment and graft rejection are associated with endothelial dysfunction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0803-7051
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
162-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10855741-Animals, pubmed-meshheading:10855741-Blood Pressure, pubmed-meshheading:10855741-Body Weight, pubmed-meshheading:10855741-Chronic Disease, pubmed-meshheading:10855741-Drug Therapy, Combination, pubmed-meshheading:10855741-Graft Rejection, pubmed-meshheading:10855741-Heart Rate, pubmed-meshheading:10855741-Hypertension, pubmed-meshheading:10855741-Hypertrophy, Left Ventricular, pubmed-meshheading:10855741-Immunosuppressive Agents, pubmed-meshheading:10855741-Kidney, pubmed-meshheading:10855741-Kidney Transplantation, pubmed-meshheading:10855741-Male, pubmed-meshheading:10855741-Mesenteric Arteries, pubmed-meshheading:10855741-Nephrectomy, pubmed-meshheading:10855741-Postoperative Complications, pubmed-meshheading:10855741-Rats, pubmed-meshheading:10855741-Rats, Inbred BN, pubmed-meshheading:10855741-Rats, Inbred Strains, pubmed-meshheading:10855741-Reference Values, pubmed-meshheading:10855741-Transplantation, Homologous
pubmed:year
2000
pubmed:articleTitle
Development of chronic allograft rejection and arterial hypertension in Brown Norway rats after renal transplantation.
pubmed:affiliation
Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland. timo.vaskonen@helsinki.fi
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't