Cardiac Aldosterone Production in Genetically Hypertensive Rats

Abstract

Abstract-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. (Hypertension. 2000;36:495-500.)Key Words: heart Ⅲ rats, inbred strains Ⅲ aldosterone Ⅲ hypertrophy Ⅲ cytochrome p450 Ⅲ mRNA A ldosterone receptors are present in cardiac myocytes, endocardial endothelial cells, and cardiac fibroblasts. 1 The peripheral infusion of aldosterone in rats causes cardiac hypertrophy and cardiac fibrosis without increasing the blood pressure. 2 In cultured neonatal rat fibroblasts or cardiomyocytes, aldosterone increases collagen synthesis and protein synthesis. 3,4 Physiologically significant amounts of mineralocorticoids are believed to be synthesized only in the adrenal cortex. However, extra-adrenal steroid 21-hydroxylation and 11␤-hydroxylation occur in a variety of human tissues. Circulating progesterone is converted to deoxycorticosterone (DOC) and DOC sulfate in adult and fetal human extra-adrenal tissues. 5 The extra-adrenal expression of steroid 21-hydroxylase and 11␤-hydroxylase by a benign testicular Leydig cell tumor has also been reported. 6 We reported that aldosterone, synthesized in the vasculature, is in part controlled by angiotensin (Ang) II and participates in the development of vascular hypertrophy that correlates with Ang II concentration. 7,8 We performed the present study to determine whether the rat heart produces aldosterone and to investigate the effects of adrenalectomy, ACE inhibitor, and Ang ...

Cardioprotective Effects of Eplerenone in the Rat Heart

“…In some of our experiments, aldosterone was detectable in coronary effluent, obtained during the 30 minutes of perfusion with vehicle before the collection of the heart. Although this could reflect local synthesis of aldosterone, 12 it might also represent washout of blood-derived aldosterone that had accumulated in the heart in vivo.…”

“…7,9,10 In the heart, it has been proposed that the presence of such high levels depend on local synthesis of aldosterone, although not all of the studies agree on this issue. [11][12][13] Across the human coronary vascular bed, both release and uptake of aldosterone have been observed. 14,15 In the present study, using the isolated perfused rat Langendorff heart, we first investigated whether the new and more selective MR antagonist eplerenone exerts the same cardioprotective effects as spironolactone, to additionally unravel whether these effects are MR mediated.…”

Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice

“…13 The synthesis of aldosterone requires the aldosterone synthetase CYP11B2. 33 Several reports have shown that there isCYP11B2 mRNA expression and activity in the heart and vessel walls; 34 however, results regarding the synthesis of aldosterone in the heart and peripheral vasculature are contradictory. 35 We tried to examine the mRNA expression levels of CYP11B2 in the heart, aorta and kidney using quantitative real-time PCR, but we could not detect the expression of CYP11B2 in any tissues (data not shown).…”

Effects of Eplerenone and Salt Intake on Left Ventricular Remodeling after Myocardial Infarction in Rats

“…It has been reported that aldosterone synthesis in local cardiac tissues and its effects are related with the process of left ventricular remodeling (26). Aldosterone blockers have been reported to suppress cardiac hypertrophy and cardiac fibrosis (27,28). Takeda et al reported that a high-salt intake accelerates the expression of the aldosterone synthase gene, CYP11B2 mRNA, in the cardiac tissues while also increasing cardiac aldosterone synthesis locally, which may affect cardiac hypertrophy independently of the RAAS in blood (29).…”