Immunosuppressant HR-325 attenuates progression of malignant arteritis in the kidney of Dahl salt-sensitive rats.
We investigated the effects of the immunosuppressant HR-325 on arterial lesions in Dahl rats with salt-induced hypertension. Forty-eight 6-wk-old Dahl salt-sensitive (DS) rats were divided into 1) a low-salt (0.3% NaCl) group, 2) a high-salt (4% NaCl) group, 3) a high-salt and low-dose (1 mg/kg) HR-325 group, and 4) a high-salt and high-dose (30 mg/kg) HR-325 group. The rats were treated for 8 wk. Various variables of renal function and morphological alterations in the kidney were assessed. Blood pressure was measured by the tail-cuff method. HR-325 significantly decreased systolic blood pressure in a dose-dependent manner throughout the study. HR-325 tended to decrease plasma creatinine level and increase creatinine clearance rate. Morphological studies revealed that HR-325 treatment strikingly resolved infiltration of immune-related cells in perivascular and intraluminal lesions, thereby decreasing the total arterial injury score by 32%. High-dose HR-325 also attenuated glomerulosclerosis and tubular injury by 35% and 34%, respectively, as compared with untreated high-salt Dahl S rats. Reduced levels of immune-related cells resulted in a decrease in urinary nitrite excretion. These data indicate that long-term treatment with the immunosuppressant HR-325 decreases systolic blood pressure in Dahl salt-sensitive rats, and that this decrease is associated particularly with resolution of infiltration of immune-related cells in arterial lesions. Hyperimmune state is responsible in part for the susceptibility of Dahl S rats to hypertensive organ damage.
Uehara
Y
Y
Second Department of Medicine, University of Tokyo, Japan.
Hirawa
N
N
Kawabata
Y
Y
Akie
Y
Y
Ichikawa
A
A
Funahashi
N
N
Omata
M
M
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001167:Arteritis / Q000188:drug therapy* / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D003401:Creatine / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000032:analysis*; D051381:Rats; D012077:Renal Artery / Q000187:drug effects* / Q000473:pathology
D000814:Aniline Compounds; C107042:HR 325; D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D003401:Creatine