Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.
This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.
Kobori
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Ichihara
A
A
Suzuki
H
H
Takenaka
T
T
Miyashita
Y
Y
Hayashi
M
M
Saruta
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001769:Blood / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006980:Hyperthyroidism / Q000150:complications*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009392:Nephrectomy; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013563:Sympathectomy, Chemical; D013777:Tetrazoles / Q000494:pharmacology; D013974:Thyroxine / Q000494:pharmacology
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D009529:Nicardipine; D019808:Losartan; D013974:Thyroxine