Abstract P082: Mitochondrial Gene Expression is Decreased in Renal Inner Medulla of Non-human Primates with Spontaneous Hypertension

Abstract

Mitochondrial gene expression may influence renal function and consequently, long-term blood pressure control. The African Green Monkey (Chlorocebus aethiops sabaeus; AGM) exhibits heritable, spontaneous hypertension and thus is a translational model for the study of human essential hypertension. We hypothesized that renal mitochondrial gene expression in hypertensive AGMs is decreased and may contribute to renal mitochondrial dysfunction in specific kidney regions. AGMs were phenotyped as normotensive (NT, systolic blood pressure; SBP <120 mmHg) or hypertensive (HT, SBP > 140 mmHg) by forearm plethysmography. Gene expression was determined using qRT-PCR with RNA extracted from renal cortex, outer medulla (OM), inner medulla (IM), and liver of 18 HT (mean SBP 166±7 mmHg) and 18 NT (mean SBP 98±3 mmHg) animals. In renal cortical and OM tissue of HT vervets, COX 3 (Complex IV), Cyt B (Complex III), NADH4 (Complex I) and ATP8 (Complex V) expression were similar in NT and HT AGMs. In IM of HT AGMs, COX3, NADH4, ATP8, and CYTB were downregulated by 4.7-fold (p=0.007), 4-fold (p=0.002), 4.1-fold (p=0.006), and 3-fold (p=0.018), respectively. In the liver, COX 3 expression was decreased 1.9-fold (p=0.04), 1.6-fold for ATP8 (p=0.03), and 2.0-fold for CYTB (p=0.01). Expression of SDH (Complex II) and COX4 (Complex IV), nuclear encoded subunits of the OXPHOS chain, was also assessed. SDH expression was up-regulated 8-fold in renal OM (p=0.005) but unchanged in liver, IM, and cortex. COX4 expression however, was down-regulated in OM by 8-fold (p=0.05), in IM by 5-fold (p=0.011) but unchanged in cortex and liver. Gene expression of the mitochondrial transcription factor TFAM was downregulated by 4-fold in renal OM, and unchanged in renal cortex and liver. Citrate synthase activity showed no difference in mitochondrial number between NT and HT AGMs (p=0.73). We suggest that reduced expression of mitochondrially encoded OXPHOS subunits in the renal IM may contribute to the development of hypertension in the AGM. Mitochondrial gene down-regulation in the liver may be a consequence of the systemic hypertension. We conclude that altered mitochondrial gene expression may be a cellular response to increased oxidative stress in the renal inner medulla of HT AGM.