Cardiac aldosterone production in genetically hypertensive rats.
Aldosterone is synthesized in extra-adrenal tissues, both blood vessels and brain. We undertook the present study to determine whether the rat heart produces aldosterone and to investigate the effects of adrenalectomy, ACE inhibition, and angiotensin II on aldosterone synthesis in the heart. To clarify the pathophysiological role of cardiac aldosterone in the hypertensive heart, we compared the synthesis of aldosterone in the hearts of stroke-prone spontaneously hypertensive rats (SHRSP) with that in Wistar-Kyoto rats. The effects of the aldosterone antagonist spironolactone on myocardial hypertrophy in adrenalectomized SHRSP were also studied. Isolated rat hearts were perfused for 2 hours, and the perfusate was analyzed with HPLC and mass spectrometry. The activity of aldosterone synthase was estimated on the basis of the conversion of [(14)C]deoxycorticosterone to [(14)C]aldosterone. The levels of aldosterone synthase gene (CYP11B2) mRNA were determined with competitive polymerase chain reaction. Aldosterone production, the activity of aldosterone synthase, and the expression of CYP11B2 mRNA were increased in hearts from adrenalectomized rats and rats treated with angiotensin II. ACE inhibitors decreased cardiac aldosterone synthesis. Cardiac aldosterone, aldosterone synthase activity, and CYP11B2 mRNA levels in hearts from 2- and 4-week-old SHRSP were significantly greater than those of age-matched Wistar-Kyoto rats. Spironolactone prevented cardiac hypertrophy in adrenalectomized SHRSP. These results suggest that the rat heart produces aldosterone and that endogenous cardiac aldosterone may affect cardiac function and hypertrophy in hypertension in rats.
Takeda
Y
Y
Second Department of Internal Medicine, Department of Health Sciences, School of Medicine, Kanazawa University, Kanazawa, Japan. takeday@mhs.mp.kanazawa-u.ac.jp
Yoneda
T
T
Demura
M
M
Miyamori
I
I
Mabuchi
H
H
D000315:Adrenalectomy; D000450:Aldosterone / Q000096:biosynthesis* / Q000097:blood; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control*; D003345:Corticosterone / Q000097:blood; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood; D013148:Spironolactone / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D012083:Renin; D003345:Corticosterone