Spontaneous Hypertension and Cardiorenal Pathologies in the African Green Monkey

Abstract

The African Green monkey (AGM), Chlorocebus aethiops sabaeus, is a highly translational non‐human primate model of spontaneous hypertension. Using forearm plethysmography under ketamine sedation (~15mg/kg), AGMs were categorized as hypertensive (HT, SBP >140mmHg), borderline hypertensive (BHT, 120mmHg < SBP < 140mmHg), or normotensive (NT, SBP < 120 mmHg). Of the 264 animals phenotyped, 32% (85 of 264) were HT (average MAP 108.2±2.2mmHg), 18% (49 of 264) were BHT (average MAP 87.5±2.0mmHg), and 49% (130 of 264) were NT (average MAP 68.6±1.3mmHg). HT animals tend to be older than NT animals (12.4±0.7 yrs vs. 8.7±0.6 yrs; p<0.05) with elevated heart rates (134.3±2.1 bpm vs. 121.6±1.9 bpm, p<0.05), similar to human essential hypertension. HT animals have increased cellular myocyte cross‐sectional area in left ventricles (1658.4±194.7 μm2) compared to NT (791.0±168.9 μm2;p<0.05, n=8) AGMs. Wall/lumen (W/L) ratios of renal arterioles (>100µm diameter) were greater in HT (0.15±0.02 vs. 0.11±0.04; p<0.05, n=8) animals. HT glomeruli have increased Bowman's capsular space (44.4±3.1% area vs. 30.9±1.9% area; p<0.05, n=5). Elevated heart rates and left ventricular hypertrophy suggest that hypertension in AGMs is driven by increased sympathetic nerve activity (SNA). Increased W/L ratios and Bowman's capsular space indicate renal vascular remodeling and altered glomerular function. This data postulates that the AGM is a model of spontaneous hypertension with elevated SNA, increased renal vascular resistance and altered glomerular capillary function. Supported by Biomedical Sciences Research Group, LLC and the Behavioural Sciences Foundation