Triphasic blood pressure responses to cannabinoids: do we understand the mechanism?

Abstract

The cannabinoids comprise three major classes of substances, including compounds derived from the cannabis plant (e.g. D 9-tetrahydrocannabinol and the chemically related substances CP55940 and HU210), endogenously formed (e.g. anandamide) and synthetic compounds (e.g. WIN55212-2). Beyond their psychotropic effects, cannabinoids have complex effects on blood pressure, including biphasic changes of D 9-tetrahydrocannabinol and WIN55212-2 and an even triphasic effect of anandamide. The differing pattern of blood pressure changes displayed by the three types of compounds is not really surprising since, although they share an agonistic effect at cannabinoid CB1 and CB2 receptors, some compounds have additional effects. In particular, anandamide is known for its pleiotropic effects, and there is overwhelming evidence that anandamide influences blood pressure via (i) CB1 receptors, (ii) TRPV1 receptors, (iii) endothelial cannabinoid receptors and (iv) degradation products. This review is dedicated to the description of the effects of externally added cannabinoids on cardiovascular parameters in vivo. First, the cardiovascular effects of cannabinoids in anaesthetized animals will be highlighted since most data have been generated in experiments of that type. The text will follow the three phases of anandamide on blood pressure, and we will check to which extent cardiovascular changes elicited by other cannabinoids show overlap with those effects or differ. The second part will be dedicated to the cardiovascular effects of the cannabinoids in conscious animals. In the third part, cardiovascular effects in humans will be discussed, and similarities and differences with respect to the data from animals will be examined.

Enhanced function of inhibitory presynaptic cannabinoid CB1 receptors on sympathetic nerves of DOCA–salt hypertensive rats

“…Like in our previous studies [12,36], we used pithed and vagotomised rats because we wanted to study peripheral mechanisms only. Cannabinoids induce complex cardiovascular changes via various peripheral and/or central receptors/mechanisms; the central effects can override the peripheral ones [24]. In our model, the electrical stimulation of the preganglionic sympathetic nerve fibres increases BP, which is predominantly associated with the release of catecholamines from neuronal endings of the resistance vessels because 10 μmol/kg prazosin diminished these responses by 95% (data not shown).…”

Effects of cannabidiol on contractions and calcium signaling in rat ventricular myocytes

“…Administration of cannabinoids, such as THC and CBD, causes complex hemodynamic changes involving phases of both increased and decreased blood pressure as well as changes in heart rate and contractility [for reviews, 10,23]. CBD has been shown to have various effects on muscular structures, neuronal and endothelial cells and alter the activities of several receptors, ion channels [for reviews, 3,9,24] and neurotransmitter transporters [24,25,26].…”

Mitogen‐Activated Protein Kinase and Intracellular Polyamine Signaling Is Involved in TRPV1 Activation–Induced Cardiac Hypertrophy

“…The present study reveals that increased expression of TRPV1 in TAC‐treated mice and activation of TRPV1 is able to induce cardiohypertrophic response in vitro. Although TRPV1 was initially identified as the receptor for CAP—the pungent ingredient in hot chili peppers—it has other functions, and multiple signals and inputs, such as pH, endogenous anandamide, protein kinase C phosphorylation, mechanosensitivity, and baroreflex, that activate TRPV1 are also associated with cardiohypertrophic conditions 25, 26, 27, 28, 29. This indicates that TRPV1 plays an important role in cardiac physiology and in the progression of cardiac hypertrophy.…”