Effect of ciclosporin on cardiac output and regional blood flow in rats: ciclosporin-induced nephropathy and its prevention with calcium channel blocker.

Abstract

The effect of ciclosporin (CS) on cardiac output (CO) and regional blood flow was studied using the microsphere method in heminephrectomized rats with and without renal arterial clamping prior to the administration of CS. The effect of a calcium (Ca) channel blocker, verapamil, was also examined on CS-induced nephropathy. CS at a dose of 40 mg/kg per day was given orally using a gastric tube for 7 days. Verapamil was given in the drinking water for 7 days. Significant increases in blood urea nitrogen (BUN) and serum creatinine (sCr) with a significant decrease in renal inulin clearance (CIn) were noted after 7 days of CS administration in both intact and ischemic-kidney groups, indicating the development of CS-induced nephropathy. The ischemic-kidney group showed a significantly severe nephropathy as compared with the intact-kidney group. As for change in CO and regional blood flow, CS caused a significant decrease in CO, renal blood flow (RBF) and brain blood flow, while hepatic arterial blood flow and muscular blood flow significantly increased. The renal outer cortical blood flow decreased markedly while the inner cortical blood flow remained unchanged. Although verapamil slightly but significantly decreased mean arterial blood pressure in CS-treated rats, CO and its distribution did not change. BUN and sCr were not significantly ameliorated in the intact-kidney group. However, in the ischemic-kidney group, verapamil caused a significant improvement in RBF, ameliorating CS-induced elevation of BUN and sCr, and a decrease in CIn.(ABSTRACT TRUNCATED AT 250 WORDS)