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 cardiac expression of renin mRNA. The present study addresses the hypothesis that renal hypertrophy in hyperthyroidism is mediated by amplification of renal expression of renin mRNA. Twenty Sprague-Dawley rats were divided into control (n=5) and hyperthyroid groups by daily intraperitoneal injections of saline vehicle or thyroxine. The hyperthyroid group was subdivided further into hyperthyroid-vehicle (n=5), hyperthyroid-losartan (n=5), and hyperthyroid-nicardipine (n=5) groups by daily intraperitoneal injections of saline vehicle, 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%). Radioimmunoassays and reverse transcriptase-polymerase chain reaction revealed increased renal renin (+91%) and angiotensin II (+65%) levels and enhanced renal renin mRNA expression (+113%) in the hyperthyroid groups. Losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced renal hypertrophy. These results suggest that thyroid hormone activates the intrarenal renin-angiotensin system via enhancement of renal renin mRNA expression, which then leads to renal hypertrophy.
Kobori
H
H
Department of Internal Medicine, School of Medicine, Keio University, 160-8582, Japan.
Ichihara
A
A
Miyashita
Y
Y
Hayashi
M
M
Saruta
T
T
D000704:Analysis of Variance; D000804:Angiotensin II / Q000032:analysis / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006980:Hyperthyroidism / Q000378:metabolism / Q000473:pathology*; D006984:Hypertrophy; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013974:Thyroxine / Q000494:pharmacology
D000959:Antihypertensive Agents; D012333:RNA, Messenger; D000804:Angiotensin II; D009529:Nicardipine; D012083:Renin; D019808:Losartan; D013974:Thyroxine