Anandamide induces cardiovascular and respiratory reflexesviavasosensory nerves in the anaesthetized rat

Abstract

1 We tested the hypothesis that sensory nerves innervating blood vessels play a role in the local and systemic regulation of the cardiovascular and respiratory (CVR) systems. We measured CVR re¯exes evoked by administration of anandamide (86 ± 863 nmoles) and capsaicin (0.3 ± 10 nmoles) into the hindlimb vasculature of anaesthetized rats. 2 Anandamide and capsaicin each caused a rapid dose-dependent re¯ex fall in blood pressure and an increase in ventilation when injected intra-arterially into the hindlimb. 3 Action of both agonists at the vanilloid receptor (VR1) on perivascular sensory nerves was investigated using capsazepine (1 mg kg 71 i.a.) a competitive VR1 antagonist, ruthenium red (1 mg kg 71 i.a.), a non-competitive antagonist at VR1, or a desensitizing dose of capsaicin (200 nmoles i.a.). The cannabinoid receptor antagonist SR141716 (1 mg kg 71 i.a.) was used to determine agonist activity at the CB 1 receptor. 4 Capsazepine, ruthenium red, or acute VR1 desensitization by capsaicin-pretreatment, markedly attenuated the re¯ex CVR responses evoked by anandamide and capsaicin (P50.05; paired Student's t-test). Blockade of CB 1 had no signi®cant e ect on the responses to anandamide. 5 Local sectioning of the femoral and sciatic nerves attenuated CVR responses to anandamide and capsaicin (P50.05). Vagotomy or carotid sinus sectioning had no signi®cant e ect on anandamideor capsaicin-induced responses. 6 These data demonstrate that both the endogenous cannabinoid, anandamide, and the vanilloid, capsaicin, evoke CVR re¯exes when injected intra-arterially into the rat hindlimb. These responses appear to be mediated re¯exly via VR1 located on sensory nerve endings within the hindlimb vasculature.

Anandamide-Induced Depressor Effect in Spontaneously Hypertensive Rats

“…15 After baseline MAP recording for 30 minutes, capsaicin or CAPZ were given by intravenous bolus injection under anesthesia with urethane to eliminate pain perception caused by capsaicin. MAP was recorded for another 1 hour after injections.…”

The complexities of the cardiovascular actions of cannabinoids

“…However, as commented above, SR141716A has a range of actions independent of antagonism of CB 1 receptors and its inhibitory effects should be interpreted with caution. Further evidence for the potential participation of sensory nerves in the cardiovascular effects of anandamide comes from studies in anaesthetised rats which showed that intra-arterial injection of anandamide led to hypotension and increased ventilation (Smith & McQueen, 2001). These responses were mimicked by capsaicin, but inhibited by vanilloid receptor antagonists, desensitisation of vanilloid receptors and sectioning of the femoral and sciatic nerves, with the implication that they were due to sensory nerve reflexes evoked by anandamide.…”

N-methyl-D-aspartate receptors mediate Mesobuthus tamulus venominduced vasosensory reflex responses in anesthetized rats

“…[8] The venom-induced vasosensory reflex responses lasts longer than the other nociceptive agonists (capsaicin/anandamide/ αβMe-ATP)-induced responses. [6,9,10] It was also shown that nociceptive vascular reflex responses evoked by BT venom modulate cardiorespiratory parameters involving transient receptor potential vanilloid 1 (TRPV1) [11] and the efferents are located in the sympathetic and vagal parasympathetics. [12] Recently, the role of B1-kinin receptors has also been shown in the venom-induced vasosensory reflex responses.…”

“…Peripheral vascular disorders are also implicated in the long-term cardiovascular alterations and other behavioral changes [3,4] favoring our hypothesis. produces immediate hyperventilatory and hypotensive responses, [5,6] indicating the role of peripheral blood vessels in the modulation of cardiorespiratory system. However, these observations were limited for very short period (10 s) in contrast to the long lasting autonomic changes seen in the chronic vascular diseases.…”