Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.
We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.
Kobori
H
H
Department of Internal Medicine, School of Medicine, Keio University, 160-8582, Tokyo, Japan.
Ichihara
A
A
Miyashita
Y
Y
Hayashi
M
M
Saruta
T
T
D000704:Analysis of Variance; D000804:Angiotensin II / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism; D006980:Hyperthyroidism / Q000150:complications* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000032:analysis / Q000097:blood / Q000235:genetics; D012084:Renin-Angiotensin System / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013974:Thyroxine / Q000494:pharmacology
D012333:RNA, Messenger; D000804:Angiotensin II; D012083:Renin; D013974:Thyroxine