Palmitoylethanolamide Treatment Reduces Blood Pressure in Spontaneously Hypertensive Rats: Involvement of Cytochrome P450-Derived Eicosanoids and Renin Angiotensin System

  title={Palmitoylethanolamide Treatment Reduces Blood Pressure in Spontaneously Hypertensive Rats: Involvement of Cytochrome P450-Derived Eicosanoids and Renin Angiotensin System},
  author={Giuseppina Mattace Raso and Claudio Pirozzi and Roberta d'Emmanuele di Villa Bianca and Raffaele Simeoli and Anna Santoro and Adriano Lama and Francesca Di Guida and Roberto Russo and Carmen de Caro and Raffaella Sorrentino and Antonio Calignano and Rosaria Meli},
  journal={PLoS ONE},
Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid… Expand
The influence of DOCA-salt hypertension and chronic administration of the FAAH inhibitor URB597 on KCa2.3/KCa3.1-EDH-type relaxation in rat small mesenteric arteries.
Examination of the influence of deoxycorticosterone acetate-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 in rat small mesenteric arteries found KCa3.1 played a key role in the EDH-type dilator response of sMAs in normo- and hypertension. Expand
Cannabinoids in arterial, pulmonary and portal hypertension – mechanisms of action and potential therapeutic significance
More experimental and clinical studies are needed to clarify the role of endocannabinoids in hypertension, not only in the search for new therapeutic strategies but also in the context of cardiovascular effects of cannabinoids and the steadily increasing legalization of cannabis use for recreational and medical purposes. Expand
The role of soluble epoxide hydrolase in preeclampsia.
Novel anti-hypertensive agents that target sEH might be developed as therapeutics to control high blood pressure in women with preeclampsia, as well as in healthy and preeclamptic pregnant women. Expand
Endothelium-Derived Hyperpolarizing Factors: A Potential Therapeutic Target for Vascular Dysfunction in Obesity and Insulin Resistance
It is demonstrated that endothelial NO synthase inhibition significantly blunted the insulin-stimulated increase of ultrasound-assessed femoral blood flow without any changes in blood pressure and heart rate in rats, suggesting that local capillary NO bioavailability plays a key role in the regulation of insulin- Stimulated skeletal muscle capillary recruitment and glucose uptake. Expand
Naturally Occurring Cannabinoids and their Role in Modulation of Cardiovascular Health
Abstract In recent years, the role of the endocannabinoid system (ECS) in various cardiovascular conditions has been a subject of great interest. The ECS is composed of cannabinoid receptors, theirExpand
Effect of palmitoylethanolamide on inner retinal function in glaucoma: a randomized, single blind, crossover, clinical trial by pattern-electroretinogram
This study is the first to show promising effects of PEA on PERG and on quality of life in glaucoma patients and to record effects on intraocular pressure, visual field andquality of life. Expand


N-Palmitoylethanolamide protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress.
Results indicate that PEA treatment lowers blood pressure and can protect against hypertensive renal injury by increasing the antioxidant defense and anti-inflammatory response and modulating renin-angiotensin system. Expand
Soluble Epoxide Hydrolase Inhibition Lowers Arterial Blood Pressure in Angiotensin II Hypertension
It is demonstrated that increased sEH expression in the Ang II hypertensive kidney leads to increased EET hydration, and inhibition of sEH during Ang II hypertension is antihypertensive. Expand
Increases in plasma trans-EETs and blood pressure reduction in spontaneously hypertensive rats.
In summary, inhibition of sEH resulted in a twofold increase in plasma trans-EETs and reduced mean BP in the SHR, and the greater vasodilator potency of trans- vs. cis- EETs may contribute to the antihypertensive effects of SEH inhibitors. Expand
Soluble epoxide hydrolase inhibition protects the kidney from hypertension-induced damage.
It is demonstrated that soluble epoxide hydrolase (SEH) inhibition has antihypertensive and renal vascular protective effects in angiotensin hypertension and suggests that SEH inhibitors may be a useful therapeutic intervention for cardiovascular diseases. Expand
PPAR-alpha activator fenofibrate increases renal CYP-derived eicosanoid synthesis and improves endothelial dilator function in obese Zucker rats.
It is demonstrated that the PPAR-alpha agonist fenofibrate increased renal CYP-derived eicosanoids and restored endothelial dilator function in obese Zucker rats. Expand
P-450 metabolites of arachidonic acid in the control of cardiovascular function.
  • R. Roman
  • Biology, Medicine
  • Physiological reviews
  • 2002
It is likely that CYP metabolites of arachidonic acid contribute to the changes in renal function and vascular tone associated with some of these conditions and that drugs that modify the formation and/or actions of EETs and 20-HETE may have therapeutic benefits. Expand
Angiotensin II up-regulates soluble epoxide hydrolase in vascular endothelium in vitro and in vivo
  • Ding Ai, Yi Fu, +6 authors Yi Zhu
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences
  • 2007
Treatment with Ang II activates the sEH promoter through an AP-1-binding motif and is involved in the transcriptional up-regulation of sEH by Ang II in ECs, which may contribute to Ang II-induced hypertension. Expand
Linking an insect enzyme to hypertension: angiotensin II-epoxide hydrolase interactions.
Because of the close association of the angiotensin II/soluble epoxide hydrolase/epoxyeicosatrienoic acid system and blood pressure regulation, pharmacological inhibition of soluble epoxidehydrolase would be a useful approach to prevent and treat angiotensor II-induced cardiac hypertrophy and hypertension, as well as vascular impairments. Expand
Angiotensin-Converting Enzyme Inhibitor Prevents Age-Related Endothelial Dysfunction
It is suggested that the angiotensin-converting enzyme inhibitor prevents the age-related decline in EDHF-mediated hyperpolarization and relaxation in normotensive rats, presumably through an inhibition of the renin-angiotens in system. Expand
Hydrogen Sulfide-Induced Dual Vascular Effect Involves Arachidonic Acid Cascade in Rat Mesenteric Arterial Bed
The results suggest that H2S acts through EHDF release, which could activate PLA2, which in turn releases arachidonic acid leading, initially, to vasoconstriction followed by vasodilation mediated by cytochrome P450-derived metabolites. Expand