Abstract
Aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) catalyze the production of aldosterone and corticosterone, respectively, in the rat adrenal cortex. Recently, there has been some debate as to whether these corticosteroids are also produced in the hearts of rodents and humans, possibly contributing to the development of hypertrophy and myocardial fibrosis. To investigate this, we have used our established, highly sensitive real-time quantitative RT-PCR method to measure CYP11B1 and CYP11B2 mRNA levels in adrenal and cardiac tissue from several rat models of cardiovascular pathology. We have also studied isolated adult rat ventricular myocytes treated with angiotensin II and ACTH. Total RNA was isolated from the adrenal and cardiac tissue of 1) male Wistar rats with heart failure induced by coronary artery ligation and sham-operated controls; 2) stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats as controls; 3) cyp1a1Ren-2 transgenic rats and Fischer controls; 4) isolated adult Sprague-Dawley ventricular myocytes incubated with 11-deoxycorticosterone (DOC), DOC plus angiotensin II, or DOC plus ACTH. Adrenal CYP11B2 expression was significantly increased in transgenic rats compared with Fischer controls (1.3 x 10(9)+/- 1.2 x 10(9) vs. 2.1 x 10(7) +/- 7.0 x 10(6) copies/microg RNA; P < 0.05). There were no other significant differences in adrenal CYP11B2 or CYP11B1 expression between the model animals and their respective controls. Cardiac CYP11B1 and CYP11B2 mRNA transcript levels from all in vivo and in vitro groups were never greater than 100 copies per microgram total RNA and therefore too low to be detected reproducibly. This suggests that cardiac corticosteroid production is unlikely to be of any physiological or pathological significance.
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