MECHANISM OF HYPERTHYROIDISM-INDUCED RENAL HYPERTROPHY IN RATS

It is well known that renal hypertrophy is induced by hyperthyroidism; however, the mechanism is not fully understood. We recently reported that cardiac hypertrophy in hyperthyroidism is mediated by enhanced ca rdiac expression of renin mRNA. The present study addresses the hypoth esis that renal hypertrophy in hyperthyroidism is mediated by amplific ation of renal expression of renin mRNA. Twenty Sprague-Dawley rats we re divided into control (n = 5) and hyperthyroid groups by daily intra peritoneal injections of saline vehicle or thyroxine. The hyperthyroid -vehicle (n = 5), hyperthyroid-losartan (n = 5), and hyperthyroid-nica rdipine (n = 5) groups by daily intraperitoneal injections of saline v ehicle, losartan, or nicardipine. All rats were killed at 4 weeks, and the blood and kidneys were collected. The kidney-to-body weight ratio increased in the hyperthyroid groups (+34%). Radio-immunoassays and r everse transcriptase-polymerase chain reaction revealed increased rena l renin (+91%) and angiotensin II (+65%) levels and enhanced renal ren in mRNA expression (+113%) in the hyperthyroid groups. Losartan and ni cardipine decreased systolic blood pressure to the same extent, but on ly losartan caused regression of thyroxine-induced renal hypertrophy. These results suggest that thyroid hormone activates the intrarenal re nin-angiotensin system via enhancement if renal renin mRNA expression, which then leads to renal hypertrophy.