A18878 Circular RNA expression is reset by brief antihypertensive treatment in spontaneously hypertensive rats (SHR)

Abstract

Objectives: The ‘legacy effect’ of persistently lower blood pressure in SHR is observed after short-term treatment with angiotensin converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) antihypertensive drugs and is associated with changes in renal function. This presumably involves resetting of the genetic program leading to hypertension in SHR. Circular RNAs (circRNA) are novel non-coding RNAs that regulate mRNA expression post-transcriptionally and might be relevant to the legacy effect. Our aim was to study circRNA expression in the SHR after antihypertensive treatment. Methods: We treated male SHR with an ACEi (perindopril), an angiotensin II receptor blocker (losartan) or a vasodilator (hydralazine) from 10–14 weeks of age. Renal cortex and cardiac left ventricular tissues were collected at 20-weeks of age (n = 3–5 per group). We measured the expression of heart related circular RNA (Hrcr), circular titin (cTtn) and circular foxhead box O3 (cFoxo3) using quantitative real-time PCR. These circRNAs have been implicated in cardiac hypertrophy and heart failure in mice. Statistical analysis was performed using one-way ANOVA and significance was set as P < 0.05. Results: Hrcr and cFoxo3 were downregulated in renal cortex at 20-weeks when compared with vehicle after all antihypertensive treatments (P < 0.01 for all). However, renal cortical cTtn expression was upregulated only after treatment with ACEi (P < 0.05) or ARB (P < 0.05). Differences in circRNA expression were not observed in heart tissues. Conclusion: Early antihypertensive treatment in SHR resets circRNA expression in renal cortices of SHR but not in the heart. This indicates tissue-specific regulation of circRNA expression might be important in reprogramming genetic hypertension by early renin-angiotensin system blocking drugs in SHR.