Abstract P010: Specific Renal Outer Medulla Upregulation of α-and β-Adrenergic Receptor Subtypes in Spontaneously Hypertensive African Green Monkeys

Abstract

The African Green Monkey ( Chlorocebus aethiops sabaeus ) is a highly translational model of spontaneous hypertension (HT). Within the cohort of measured colony animals, 33% (98 of 300) of adult African Green Monkeys exhibit systolic blood pressures (SBP)> 140 mmHg, assessed by forearm cuff plethysmography. Heart rate is elevated in HT vs. normotensive (NT) animals (121±2 bpm vs. 134±2 bpm, p<0.05) suggesting that sympathetic nerve activity is likely elevated in the HT African Green Monkey, similar to patients with essential hypertension. This study assessed mRNA expression of adrenergic receptor subtypes in the renal cortex, outer medulla, and inner medulla of male HT and NT African Green Monkeys. Primers were custom designed and evaluated for appropriate specificities and efficiencies (95-105%) for α 1a , α 1d , α 2c , β 1 and β 2 adrenoceptors. Gene expression was measured with qRT-PCR and normalized to RPS32 expression in the liver of each animal. The HT cohort of African Green Monkeys (n=18) assessed an averaged SBP of 168.24 ± 7.25mmHg compared with NT animals (n=18) that averaged 96.61 ± 3.20mmHg. Expression of α 1a , α 1d and α 2c genes were all increased in the renal outer medulla of HT animals (α 1a : NT RQ 0.24 ± 0.15 vs. HT RQ 0.89 ± 0.22, p<0.05; α 1d : NT RQ 0.43 ± 0.24 vs. HT RQ 1.99 ± 0.74, p<0.05; and α 2c : NT RQ 1.11 ± 0.53 vs HT RQ 1.41 ± 0.35, p<0.05). β 1 adrenergic receptor expression in the outer medulla was similar in NT and HT animals (β 1 : NT RQ 0.75 ± 0.30 vs. HT RQ 1.82 ± 0.64, p>0.05), but β 2 adrenoceptor expression was upregulated in HT animals (β 2 : NT RQ 0.36 ± 0.13 vs HT RQ 2.05 ± 0.82; p<0.05). Expression of each adrenoceptor subtype was similar in the renal cortex and inner medulla of HT animals (p>0.05, all groups compared with Mann-Whitney U Test). These data suggest that the renal outer medulla of HT African Green Monkey may be sensitized to sympathetic nerve activity via elevated adrenergic receptor gene expression. Thus, subtle changes in renal sympathetic outflow may elicit renal medullary vasoconstriction and contribute to the development of the spontaneous hypertensive phenotype in the African Green Monkey.