INVESTIGATOR: Zhi-Ling Guo, M.D., Ph.D.
STUDY LOCATION: UC Irvine
PROJECT TITLE: Sex differences in cannabidiol’s effects on blood pressure in normotensive and hypertensive conditions
FUNDING SOURCE: Center for Medicinal Cannabis Research
PROJECT TYPE: Pre-Clinical Study
STATUS: Active
ABSTRACT:
Cannabidiol (CBD) is used to manage many clinical disorders. However, little is known about its effects on cardiovascular functions in normotensive and hypertensive conditions in different sexes. Despite different profiles of hypertension in different sexes, it remains unknown whether sex is a factor contributing to CBD’s influence on blood pressure (BP). Mechanical (e.g., gastric distension) stimulation of sympathetic nerves in viscera commonly causes pain and pressor cardiovascular responses, leading to increased morbidity and mortality, especially in patients with cardiovascular diseases. However, no information is available on whether CBD can modulate those pressor responses. Previous studies showed CBD’s antidepressant effects in males only. Estrogen dampens central cannabinoid-mediated cardiovascular response in female rats. These findings imply sex differences in CBD’s efficacy and an inhibitory impact of estrogen on CBD. Determining sex’s influence on CBD’s effects on cardiovascular functions will provide significant insight into CBD’s clinical application. The goal of the proposed study is to examine whether there are differences between sexes in CBD’s effects on cardiovascular functions in normotensive and hypertensive conditions and an acute reflex increase in BP. The specific aims will be studied in rats as follows. Dahl salt-sensitive rats will be fed a high-salt diet to induce hypertension, mimicking essential human hypertension. Aim 1 will test CBD’s effects on cardiovascular functions in normotensive rats of both sexes. Aim 2 will examine CBD’s effects on BP and cardiovascular functions in hypertensive rats of both sexes. In Aims 1 and 2, CBD will be applied in male rats and female rats with and without ovariectomy (OVX) that results in estrogen deficiency. BP and heart rate (HR) will be measured by biotelemetry devices, and cardiac function by the micro-ultrasound system. Aim 3 will examine CBD’s effect on pressor cardiovascular responses induced by visceral stimulation in normotensive and hypertensive rats of both sexes. After artery cannulation, elevated BP and HR induced by gastric distension will be recorded before and after CBD application in male rats and female rats with and without OVX in normotensive and hypertensive conditions. In all aims, estrogen will be given in separate female rats with OVX. The new findings will shed light on CBD’s clinical application to individuals with and without hypertension.