Sex and Hypertension in the African Green Monkey, a Translational Model of Human Cardiovascular Disease
Authors: Rhoads Megan K , Weaver Chelsea C , Osborn Jeffrey L 
Published: November 2023

Hypertension, the chronic elevation of blood pressure, is a complex disease and risk factor for the development of many fatal secondary pathologies, including cardiovascular disease, heart failure, chronic kidney disease, and atherosclerosis. While many gains have been made in basic research using traditional experimental models, the underlying etiology of hypertension in bipedal primates remains unknown. We propose that Chlorocebus aethiops sabaeus, the African Green Monkey (AGM), is a novel non‐human primate model of spontaneous hypertension that closely recapitulates the phenotype of essential hypertension. Adult AGMs were lightly sedated with ketamine (~ 15mg/kg) and blood pressure measured using forearm cuff plethysmography. Animals with systolic blood pressure (SBP) > 140 mmHg were categorized as hypertensive (HT) and those with SBP < 120mmHg were categorized as normotensive (NT). AGMs with SBP < 140mmHg or >120mmHg are considered borderline hypertensive (BHT). NT animals (n=187/424, 44%) had an average mean arterial pressure (MAP) of 70.8±1.0 mmHg while BHT (n=80/424, 19%) had an average MAP of 89.4±1.5 mmHg. HT AGMs (n=157/424, 37%) have an average MAP of 112.2±1.7 mmHg. Males (n=307) and females (n=117) have similar MAPs within phenotypic group (ex. Male NT MAP = 68.8±1.2 vs. female NT MAP = 75.3±3.9, p>0.05, Bonferroni post hoc) and have a similar prevalence of hypertension (p>0.05, Fisher's test). Heart rate (HR) is increased in HT animals (137.7±2.2 bpm) compared to NT animals (125.7±2.0 bpm, p<0.05, Bonferroni post hoc). Between the sexes, HR is increased within each phenotypic group (NT males: 117.3±2.0 bpm vs. NT females: 144.9±3.9 bpm; BHT males: 128.2±2.5 bpm vs. BHT females: 164.5±6.3 bpm; HT males: 130.3±2.0 bpm vs. HT females: 162.3 ±4.9 bpm, p<0.05). Adult males are larger than females (overall: 5.4 ±0.1 kg vs. 3.5±0.1 kg, p<0.05), regardless of phenotypic blood pressure group. MAP is positively correlated with SBP (Pearson's correlation coefficient, PCC: 0.852, p<0.05), diastolic blood pressure (PCC: 0.912, p<0.05), HR (PCC: 0.247, p<0.05), and age (PCC: 0.196, p<0.05). MAP is not correlated with body weight (PCC: 0.57, p>0.05). These data highlight many similarities to human essential hypertension in this spontaneous non‐human primate model. These animals are not bred specifically for the presence of this pathology, nor do they exhibit dietary induced chronic elevation of blood pressure. Females have elevated heart rates compared to males and are smaller in size, but there is no significant difference in the prevalence of hypertension between the sexes. It is likely that age (pre‐ vs. post‐menopause) plays a role in the development of hypertension in females, similar to human patients, but more longitudinal data needs to be collected in order to test this assumption. The African Green Monkey is a highly translational bipedal model available to the scientific community as a source of new targets and therapies in the study of complex human cardiovascular and related diseases.

Support or Funding Information

This work is supported by an American Heart Association Predoctoral Fellowship and Biomedical Science Research Group, LLC.