ABSTRACT
BACKGROUND AND PURPOSE: Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone. We aimed to evaluate the influence of superior mesenteric artery (SMA) ischaemia-reperfusion (I/R) on mesenteric resistance artery vasomotor function and the mechanism involved in the changes in vascular responses to ET-1. EXPERIMENTAL APPROACH: SMA from male Sprague-Dawley rats was occluded (90 min) and following reperfusion (24h), mesenteric resistance arteries were dissected. Vascular reactivity was studied using wire myography. Protein and mRNA expression, superoxide anion (O(2) (â¢-) ) production and ET-1 plasma concentration were evaluated by immunofluorescence, real-time quantitative PCR, ethidium fluorescence and elisa, respectively. KEY RESULTS: I/R increased ET-1 plasma concentration, ET-1-mediated vasoconstriction and ET(B) mRNA expression, and down-regulated ET(A) mRNA expression. Immunofluorescence confirmed mRNA results and revealed an increase in ET(B) receptors in the mesenteric resistance artery media layer after I/R. Therefore, the ET(B) receptor agonist sarafotoxin-6 induced a contraction that was inhibited by the ET(B) receptor antagonist BQ788 only in vessels, with and without endothelium, from I/R rats. Furthermore, BQ788 potentiated ET-1 vasoconstriction only in sham rats. Endothelium removal in rings from I/R rats unmasked the inhibition of ET-1 vasoconstriction by BQ788. Endothelium removal, N(ω) -nitro-L-arginine methyl ester and superoxide dismutase abolished the differences in ET-1 vasoconstriction between sham and I/R rats. We also found that I/R down-regulates endothelial NOS mRNA expression and concomitantly enhanced O(2) (â¢-) production by increasing NADPH oxidase 1 (NOX-1) and p(47phox) mRNA. CONCLUSIONS AND IMPLICATIONS: Mesenteric I/R potentiated the ET-1-mediated vasoconstriction by a mechanism that involves up-regulation of muscular ET(B) receptors and decrease in NO bioavailability.
Subject(s)
Endothelin-1/physiology , Ischemia/physiopathology , Mesenteric Arteries/physiology , Reperfusion , Vasoconstriction/physiology , Acetylcholine/pharmacology , Animals , Cyclooxygenase Inhibitors/pharmacology , Endothelin-1/blood , Free Radical Scavengers/pharmacology , In Vitro Techniques , Indomethacin/pharmacology , Male , Myocytes, Smooth Muscle/physiology , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/physiology , Nitric Oxide Synthase Type III/antagonists & inhibitors , Nitric Oxide Synthase Type III/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Endothelin A/physiology , Receptor, Endothelin B/physiology , Superoxide Dismutase/pharmacology , Superoxides/metabolismABSTRACT
The cultivated species of the wild autochthonous Asparagus officinalis in Andalusia in Spain is commonly called "triguero" asparagus. This vegetable has traditionally been very much appreciated for its organoleptic and nutritional characteristics. This study has been designed to evaluate the potential effect of different concentrations of freeze-dried asparagus (500, 250, and 125 mg/Kg of body weight/day) on oxidative status and lipid profile in rats fed a cholesterol-rich diet. After five weeks of treatment, doses of 250 and 500 mg/Kg of asparagus were able to significantly reduce total cholesterol and LDL cholesterol levels. Atherogenic index was also significantly reduced in a dose-dependent manner by administrating freeze-dried asparagus. A beneficial effect was observed in the HDL cholesterol levels in asparagus-fed groups although the increase was not significant. Consumption of asparagus also improved antioxidant status, assayed superoxide dismutase (SOD) and catalase (CAT) enzymes, and protected against lipid peroxidation. These results show that the intake of green asparagus from Andalusia (Spain) helps to regulate plasma lipid levels and prevents oxidative damage in hypercholesterolemic conditions.
