The endocannabinoid system is a neuromodulatory system that is conserved among vertebrate species. Cannabidiol (CBD) is a modulator of cannabinoid (CB) receptor action both in the central nervous system and in the periphery. CB receptors are involved in inflammatory responses in peripheral organs, including lung tissue. CBD administration has been shown to reduce airway inflammation and fibrosis in vitro and in experimentally induced rodent models of asthma through modulation of the immune system. However, little is understood regarding the relationship between pulmonary disease and CBD modulation of general CB receptors in vivo. The African Green Monkey (Chlorocebus aethiops sabaeus; AGM) has bronchiolar tissue and tracheal branching remarkably similar to that in human lungs, therefore making it a translational model for the study of CBD treatment on pulmonary fibrosis‐related lung dysfunction. We hypothesize that administration of NCMB‐1, a hemp extract with CBD, will increase the tidal volume, inspiratory flow rate, and respiration rate of animals with previously induced pulmonary fibrosis. Baseline tidal volume, inspiration flow rate, and respiration rate of 16 male AGM with induced lung fibrosis were measured. Animals were divided into a vehicle and 3 treatment groups: 50 μL of undiluted, 5X dilution, and 25X dilution NCMB‐1 administered orally twice daily via banana sections for two weeks. Compared to control (n=4, 206.6 ± 36.4 mL), 5X NCMB‐1 treated animals increased tidal volume (n=4, 484.0 ± 54.6 mL; p<0.05) from baseline at two weeks of treatment. Inspiratory flow rate also increased in 5X treated animals (n=4, 412.0 ± 49.9 mL/s; p<0.05) compared to control (n=4, 212.3 ± 50.7 mL/s) after two weeks of administration. Respiration rates increased from baseline in 1X treated animals (n=4, 33.0 ± 4.5 breaths/min) and 5X treated animals (n=4, 30.8 ± 3.9 breaths/min) compared to control (n=4, 28.5 ± 4.1 breaths/min; p<0.05). Treatment with 25X dilution of NCMB‐1 did not alter pulmonary function at either one or two weeks of treatment compared to vehicle treated animals. Thus, administration of 5X diluted NCMB‐1 to AGM with induced pulmonary fibrosis increased tidal volume, inspiratory flow rate, and respiration rate from compared to vehicle treated AGM. These results indicate CBD as a potential modulator of CB receptors improving pulmonary function and suggest a potential for therapeutic value of CBD in the treatment of restrictive pulmonary disease. Future directions include identification of active CBD compounds within the extract responsible for changes in airway resistance, expression of specific pulmonary genes involved in reduction of inflammation, and immunohistochemistry of CB receptors in the hypothalamus of AGM with induced pulmonary fibrosis. CBD crossing the blood brain barrier in animals treated with NCMB‐1 may cause up or downregulation of CB1 and/or CB2 receptors that could positively impact lung function. Support or Funding Information Funding provided by Primates Plus, LLC.
Hypertensive pregnancy disorders are the most common pregnancy complication and are a primary cause of maternal and fetal mortality worldwide. Preeclampsia (PE), defined as de novo maternal hypertension and proteinuria in the 2nd or 3rd trimester, is associated with preterm birth and long‐term cardiovascular risk in both mothers and offspring. The African Green Monkey (AGM; Chlorocebus aethiops sabaeus) develops spontaneous preeclampsia and exhibits fetal growth restriction. We hypothesize that PE pregnancies leading to reduced birthweight may increase the risk for impaired renal and metabolic function in offspring. Offspring of normotensive (NT) pregnancies averaged 335.6 ± 9.6g birthweight, while birthweight of offspring born to PE females was 299.4 ± 9.0g, indicating fetal growth restriction (NT n=12; PE n=24; pδ0.05). To assess glucose tolerance, an oral glucose tolerance test (OGTT) was conducted on a subset of offspring at 1–3 years of age. Glucose was fed to a final concentration of 1.75 g/kg bodyweight. Blood glucose was measured by finger stick with standard glucometry prior to the glucose load and at 15, 30, 60, 90, and 120 minutes post glucose load. Fasting blood glucose was similar between NT and PE juveniles (NT n=9, 77.7 ± 8.4 mg/dl; PE n=11, 82.2 ± 7.6 mg/dl; p>0.05). Blood glucose of NT juveniles peaked at 15 minutes (141.7 ± 18.9mg/dl) and subsequently decreased. In contrast, PE juveniles showed a biphasic glucose response, first peaking at 15 minutes (132 ± 13 mg/dl) and again at 60 minutes (149.4 ± 14.1 mg/dl). The area under the curve of the OGTT was used as an index of glucose tolerance. Glucose tolerance of PE juveniles was impaired compared to NT juveniles (NT n=9, 10994 ± 1390 min*mg/dl; PE n=11, 14831 ± 5761 min*mg/dl; pδ0.05). To monitor water intake and urine flow, juveniles were individually housed (NT n=9; PE n=10). After an acclimation period of 1 week, water intake and urine flow were measured for 3 consecutive days. Urinary protein excretion was greater in PE offspring (NT 152.0 ± 61.7 mg/day vs. PE 354.7 ± 55.8 mg/day; pδ0.05). Sodium excretion was similar between groups (NT 16.10 ± 3.2 mmol/day; PE 18.96 ± 2.9 mmol/day; p>0.05). However, potassium excretion was greater in PE offspring (6.19 ± 0.8 mmol/day vs. NT 2.70 ± 0.9 mmol/day; pδ0.05). Plasma creatinine was similar between offspring of NT and PE females (NT 1.74 ± 0.2 mg/dl; PE 1.65 ± 0.1 mg/dl; p>0.05). An individual with the lowest birth weight of the PE cohort (228.5g vs. mean 314.1 ± 14g) had the highest creatinine level (2.38 mg/dl vs. mean 1.65 ± 0.1 mg/dl) and elevated protein excretion (504.6 mg/day vs. mean 378.5 ± 74.7 mg/day). PE in AGMs is associated with fetal growth restriction resulting in low birthweights. Juveniles born to PE females showed impaired glucose tolerance, proteinuria, and kaliuresis. Exposure to PE in utero may predispose offspring to impaired renal and metabolic function in early adolescence. Continued monitoring of current PE juveniles and phenotyping of 2019 offspring will further assess the...
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