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Altered Renal and Circulating Renin‐Angiotensin System Does Not Cause Spontaneous Hypertension in the African Green Monkey
Author(s) -
Gutierrez Alex,
Goleva Slavina B,
Rhoads Megan K,
Weaver Chelsea Christina,
Beierwaltes William H,
Osborn Jeffrey L
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.965.15
Subject(s) - medicine , renin–angiotensin system , plasma renin activity , endocrinology , blood pressure , kidney , chemistry , renal cortex , extracellular fluid , angiotensin ii , radioimmunoassay , extracellular , biochemistry
The renin‐angiotensin system (RAS) is important in the long‐term regulation of, sodium balance, body fluid volumes and blood pressure. The African Green Monkey, (AGM, Chlorocebus aethiops sabaeus ) is a translational model of hypertension (HT) due to its close genetic similarity, behavioral activities and significant upright posture similar to humans. We hypothesized that upregulation of the RAS occurs in HT AGMs which may decrease Na + excretion leading to Na + retention and expansion of extracellular fluid volume. AGMs were phenotyped by systolic blood pressure (SBP) as HT (SBP>140 mmHg) or normotensive (NT, SBP<120 mmHg). Plasma and renal tissue samples were obtained from adult male AGMs with NT (n=26) having SBP of 98.2 ± 2.1 mmHg, HT AGMs (n=27) averaging 169.9 ± 6.1 mmHg. Plasma renin activity (PRA) and renal cortical renin content were determined by radioimmunoassay. Circulating PRA of NT (3.27 ± 0.36 ng AngI/ml/hr, n=15) and HT (3.34 ± 0.48 ng AngI/ml/hr, n=16) AGMs were not different (p>0.05). Renal cortex tissue was homogenized and incubated with excess renin substrate to measure renal cortical renin content (RCRC). Similar to PRA, RCRC of NT (10.73 ± 2.98 μg AngI/ml/hr/mg protein, n=11) and HT (8.94 ± 1.56 μg AngI/ml/hr/mg protein, n=13) AGMs were similar. Next, angiotensinogen (AGT) expression was assessed from renal cortex, outer medulla and liver using qRT‐PCR from extracted tissue RNA. Gene expression was normalized using RPS32 for kidney and RPS13A for liver. AGT expression was similar between NT and HT AGMs in the renal cortex (NT; 1 ± 0.55 vs HT; 1.74 ± 0.91), in the renal outer medulla (NT; 1 ± 0.16 vs HT; 0.59 ± 0.21) and liver (NT; 1 ± 0.14 vs HT; 1.19 ± 0.17, p > 0.05 for all tissues). To assess renal Na + handling in HT (n=4) and NT (n=3) AGMs, animals were housed individually in pens and urine collected at 24 hour intervals for 5 consecutive days. Daily urinary sodium excretion of HT AGM's was greater than that of NT animals (HT; 2.86±0.40 mmol/day vs NT; 1.17±0.16 mmol/day, p<0.05) but urine osmolality was not different. The similar quantities of plasma and tissue renin, combined with unchanged gene expression of AGT, indicate that renin activity and renin substrate (angiotensinogen) in the RAS do not contribute to hypertension in the AGM. Thus, the long term altered blood pressure regulation and hypertension may result from elevated peripheral resistance due to other pressor mechanisms, as our data rules out any abnormal expression or activity of the renin‐angiotensin system in this nonhuman primate model of heritable, genetic hypertension. Support or Funding Information Supported by American Physiological Society, National Heart, Lung and Blood Institute (NHLBI; 1 R25 HL115473‐01), and Biomedical Science Research Group, LLC.