Additive effects of combined valsartan and spironolactone on cardiac aldosterone escape in spontaneously hypertensive rats.
The additive effects of combined valsartan and spironolactone on plasma and cardiac aldosterone escape were evaluated in spontaneously hypertensive rats (SHRs). Twenty-four SHRs were treated with valsartan (30 mg/kg body weight per day), spironolactone (20 mg/kg body weight per day) and a combination of both for 4 months. Blood was collected and plasma aldosterone (PA) was estimated with radioimmunoassay (RIA). Ex vivo heart perfusion was performed, the ex vivo cardiac aldosterone (EXCA) was assessed by RIA after high-performance liquid chromatography separation. PA and EXCA were significantly decreased after one month but increased after 4 months in valsartan administration group. The combined valsartan and spironolactone therapy normalized cardiac aldosterone levels. This study provides the first evidence that the long-term treatment with Angiotensin II type 1 receptor antagonist (AT1A) induces local aldosterone escape in cardiovascular tissue, whereas the combined AT1A and spironolactone therapy inhibits the escape in hypertensive rats.
Liang
Y H
YH
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan city, Hubei province, 430060, PR China. ejintian@yahoo.com.cn
Wang
J M
JM
Zhou
Y
Y
Jiang
X J
XJ
Jiang
H
H
Huang
C X
CX
D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects; D013148:Spironolactone / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000068756:Valsartan
D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D013777:Tetrazoles; D013148:Spironolactone; D000450:Aldosterone; D000068756:Valsartan; D003094:Collagen; D014633:Valine; D006909:Hydroxyproline