Mechanisms of l-alpha-lysophosphatidylinositol-induced relaxation in human pulmonary arteries.

Aims: l-Alpha-lysophosphatidylinositol (LPI) is an endogenous agonist of G protein-coupled receptor 55 (GPR55) which relaxes mesenteric arteries on activation. The aim of the present study was to determine the influence and underlying mechanisms of LPI-induced relaxation in human pulmonary arteries (hPAs).

Main Methods: Functional studies were performed in isolated hPAs using organ bath technique.

Endocannabinoids modulate G protein-coupled receptor agonist-induced vasoconstriction via a negative feedback mechanism.

Objectives: The endocannabinoid (eCB) system centrally and peripherally regulates cardiovascular parameters, including blood pressure, in health and disease. The relationship between G protein-coupled receptor activation, regulation of eCBs release (mainly 2-arachidonoylglycerol) and subsequent CB receptor activation was initially observed in the central nervous system. Here, we review the latest findings from systemic physiological studies which include for the first time data from pulmonary arteries.

The influence of DOCA-salt hypertension and chronic administration of the FAAH inhibitor URB597 on K2.3/K3.1-EDH-type relaxation in rat small mesenteric arteries.

The aim of this study was to examine the influence of deoxycorticosterone acetate-salt (DOCA-salt) hypertension and chronic treatment with the fatty acid amide hydrolase inhibitor, URB597, on small and intermediate conductance calcium-activated potassium channels and endothelium-dependent hyperpolarization (K2.3/K3.1-EDH) in rat small mesenteric arteries (sMAs).

Activation of CB receptors by 2-arachidonoylglycerol attenuates vasoconstriction induced by U46619 and angiotensin II in human and rat pulmonary arteries.

Recent evidence suggests that endocannabinoids acting via cannabinoid CB receptors may modulate vascular responses of various vasoconstrictors in the rodent systemic vasculature. The aim of the study was to investigate whether endocannabinoids modulate the contractile responses evoked by a thromboxane A analog (U46619), angiotensin II (ANG II), serotonin (5-HT), and phenylephrine, which stimulate distinct G protein-coupled receptors (thromboxane, ANG II type 1, 5-HT, and α-adrenergic receptors) in isolated endothelium-intact human and rat pulmonary arteries (hPAs and rPAs, respectively). The CB receptor antagonist AM251 (1 μM) and diacylglycerol lipase (2-arachidonoylglycerol synthesis enzyme) inhibitor RHC80267 (40 μM) enhanced contractions induced by U46619 in hPAs and rPAs and by ANG II in rPAs in an endothelium-dependent manner.

Protective role of cannabinoid CB1 receptors and vascular effects of chronic administration of FAAH inhibitor URB597 in DOCA-salt hypertensive rats.

Aims: This study examined whether the fall in blood pressure (BP) induced by the chronic inhibition of fatty acid amide hydrolase (FAAH) by URB597 in deoxycorticosterone acetate (DOCA-salt) hypertensive rats correlates with endocannabinoid-mediated vascular changes.

Main Methods: Functional studies were performed in isolated endothelium-intact aortas and small mesenteric arteries (sMAs) using organ bath technique and wire myography, respectively.

Key Findings: In the DOCA-salt rats, methanandamide-stimulated relaxation was enhanced in sMAs or diminished in aortas.