Spontaneous Hypertension in Nonhuman Primate African Green Monkeys Is Associated with Left Ventricular Hypertrophy Without Significant Cardiac or Aortic Fibrosis
Authors: Gutierrez Anthony , Weaver Chelsea Christina , Osborn Jeffrey 
Published: November 2023

The African Green Monkey (AGM; Chlorocebus aethiops sabeus) develops hypertension in approximately 35% of individuals. It is likely that this hypertension is associated with elevated sympathetic nerve activity since hypertensive (HT) AGMs have significantly elevated heart rates compared to normotensive (NT) animals. Thus, hypertension in the AGM may exhibit elevated total peripheral resistance and increased cardiac after load that would lead to elevated left ventricular end systolic pressure. We hypothesize that in AGMs, chronic spontaneous hypertension elicits significant left ventricular hypertrophy (LVH), and increased myocardial and/or aortic collagen deposition compared with NT AGMs. Sedated AGMs were characterized as either HT (SBP≥140mmHg) or NT (SBP<120mmHg) using forearm plethysmography (ketamine HCl, 15 mg/kg i.m.). Cardiac and aortic tissues were obtained immediately following euthanasia (Na+ pentobarbital overdose; 150 mg/kg i.v.). Cardiac and aortic tissues were fixed with paraformaldehyde (5%) and stored in ethanol (70%) or rapidly frozen and stored at −20 °C in isopentane. Fixed ventricular and aortic cross sections were cut (5 μm), mounted and stained with hematoxylin and eosin. Randomly selected colony HT AGMs had increased left ventricular myocardial cell area compared with NT animals (1658± 515 μm2, n=6, HT vs. 791± 210 μm2, n=7, NT; p<0.01). Ventricular and aortic fibrosis was assessed using picosirius red stain which selectively identifies collagen deposition in tissue. Average area of collagen was greater in HT compared to NT AGMs (55.27 ± 2.33%, n=9 NT vs. 66.12 ± 4.22%, n=6 HT; p<0.05). No difference was measured in average area of collagen per left ventricular myocardial tissue area between HT and NT AGMs (12.22 ± 0.80%, n=10 NT vs. 14.17 ± 3.29%, n=9 HT; p=0.84). Next, total tissue collagen was measured by quantifying tissue hydroxyproline from frozen aorta and left ventricular myocardium. Collagen content between HT and NT AGMs were not different in aorta (745.64 ± 44.49 μg/ml, n=11 HT vs. 668.39 ± 31.06 μg/ml, n=11 NT, p=0.17) or in left ventricular myocardium (194.02 ± 8.61 μg/ml, n=11 HT vs. 201.70 ± 18.89 μg/ml, n=10 NT, p=0.71). These results demonstrate that chronic elevation of blood pressure in AGM is associated with LVH. Despite this LVH in hypertensive AGM, collagen biosynthesis and deposition within aorta and left ventricular myocardium is similar to NT control animals. We conclude that AGMs with chronic elevation of arterial pressure develop LVH likely from increased after load arising from increased total peripheral resistance. This LVH however, must develop in response to factors other than increased deposition of intercellular collagen. Ongoing experiments in HT AGMs will assess the deposition of other intercellular connective proteins in both left ventricle and aorta as well as the presence of pro‐inflammatory cytokines known to contribute to LVH in other experimental models of hypertension.Support or Funding InformationSupported by American Physiological Society, National Science Foundation Integrative Organismal Systems Award No. IOS‐ 1238831, and Biomedical Science Research Group, L.L.C.