Session: MON 723-757-Renin-Angiotensin-Aldosterone System/Endocrine Hypertension
Bench to Bedside
Poster Board MON-752
Methods: Adrenal glands and blood were collected from 11-week old Sprague-Dawley rats fed with either normal salt diet (NS) or SDef for 3 days. Blood was used for measurement of serum aldosterone. Adrenal glands were used for immunohistochemistry and laser-capture microdissection. Laser-captured samples were used for microarray analysis (Affimetrix).
Results: Serum aldosterone was much higher in SDef (792.4 ± 503.7 pg/mL) than in NS (55.3 ± 41.3 pg/mL, p<0.01). Immunohistochemistry showed that both NS and SDef rats had aldosterone synthase (CYP11B2, essential for aldosterone production) positive cell layers beneath the adrenal capsule. Therefore, we laser-captured an enriched population of CYP11B2-positive cells from the zG of both NS and SDef rats, as described previously 2. Although not statistically significant, microarray showed an enrichment of Cyp11b2 mRNA in SDef zG compared to NS zG (1.4x). In addition, the microarray analysis indicated that 79 transcripts were up-regulated in SDef. Interestingly, most of the up-regulated transcripts were involved in cell cycle regulation and/or proliferation. The 5 transcripts with the greatest up-regulation were cyclin-dependent kinase inhibitor 3 (11.6x); ribonucleotide reductase M2 (7.2x); topoisomerase (DNA) II alpha (6.1x); proline rich 11 (6.0x); and TPX2, microtubule-associated, homolog (5.8x).
Summary and Conclusions: We defined the zG transcripts involved in RAS activation of aldosterone synthesis following 3 days of SDef. Most activated genes were associated with cell proliferation. These transcripts may have important roles in zG expansion.
Nothing to Disclose: KN, RBSH, WER, TS
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