Influence of carvedilol on chronic renal failure progression in spontaneously hypertensive rats with adriamycin nephropathy.
BACKGROUND
In this study, the effects of carvedilol, antihypertensive (alpha-beta blocker) agent with antiproliferative and antioxidative properties, on slowing down of chronic renal failure (CRF) progression in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy were examined.


METHODS
Eighty adult (24 weeks) SHR were divided into four groups:


METHODS
20 SHR; ADR group: 20 SHR treated with ADR (2 mg/kg i.v. twice in 20 days); ADR-C group: 20 SHR treated with ADR and with carvedilol (30 mg/kg/day); ADR-CC group: 20 SHR treated with carvedilol and captopril (60 mg/kg/day). Systolic blood pressure was measured every two weeks, renal blood flow (RBF), mean arterial pressure (MAP) and renal vascular resistance (RVR) were determined at Weeks 6 and 12, creatinine clearance and proteinuria at Weeks -3 (see measurements), 6 and 12. The rats were sacrificed at Weeks 6 and 12 after the second ADR injection. Glomerular sclerosis, tubulointerstitial and blood vessel changes were determined by semiquantitative scoring.


RESULTS
Carvedilol decreased systolic blood pressure. It decreased RVR and MAP, and increased RBF significantly. Carvedilol also significantly decreased interstitial infiltration in the early phase of the study, slowed down the development of interstitial fibrosis and tubular atrophy and decreased blood vessel changes. The hemodynamic and morphological effects of carvedilol were associated with slowing down the CRF progression as well as a mild decrease in proteinuria. Captopril addition to carvedilol improved its effects especially on prevention of tubulointerstitial changes.


CONCLUSIONS
Results of this experimental study showed beneficial effect of carvedilol and its combination with captopril on CRF progression, indicating that clinical studies are warranted.
Jovanovic
D
D
Clinic of Nephrology, Clinical Centre of Serbia, Serbia and Montenegro. dijanaj@EUnet.yu
Jovovic
D
D
Mihailovic-Stanojevic
N
N
Miloradovic
Z
Z
Dimitrijevic
J
J
Maksic
N
N
Djukanovic
L
L
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D004195:Disease Models, Animal; D018450:Disease Progression; D004317:Doxorubicin / Q000633:toxicity; D004359:Drug Therapy, Combination; D005260:Female; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D009393:Nephritis / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D011412:Propanolamines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
D000903:Antibiotics, Antineoplastic; D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D004317:Doxorubicin; D002216:Captopril