The protective effects of resveratrol and L-NAME on visceral organs following aortic clamping.

BACKGROUND: This study investigated the effect of temporary occlusion of the aorta on the development of ischemia-reperfusion (I/R) injury of the visceral organs, the optimal timing of administration of resveratrol, and its mechanism of protection via inhibiting nitric oxide (NO) release with an NO synthase inhibitor. METHODS: Rabbits were divided into seven groups according to the administration period of resveratrol and/or N(G)-nitro-L-arginine methyl ester (L-NAME): control group; group 1, resveratrol during ischemic period; group 2, resveratrol during reperfusion period; group 3, L-NAME during ischemic period; group 4, L-NAME during reperfusion period; group 5, resveratrol during ischemic period and L-NAME during reperfusion period; group 6, L-NAME during ischemic period and resveratrol during reperfusion period. The infrarenal aorta was clamped for 30 min. Blood samples were taken for the biochemical assessment, and organ specimens were taken for pathological assessment at 24hr of reperfusion. RESULTS: In groups 5 and 6, the renal I/R injury was comparatively milder (I/R injury score 1.04+/-0.29 in control group, 0.25+/-0.17 in group 5, and 0.33+/-0.13 in group 6 [p<0.05]). The I/R injury of bowel was milder in group 5 (I/R injury score 1.8+/-0.80 in control group vs. 0.0+/-0.0 in group 5 [p<0.05]). CONCLUSION: The protective effects of resveratrol on organs that have high metabolic rate like kidney and bowel was proven histopathologically. It may be beneficial to use different pharmacological medications in different periods of the I/R damage as they represent different characteristics with and without oxygen. The combination of resveratrol and L-NAME against I/R injury appears to be an effective option in the near future.

Endothelium-dependent induction of vasorelaxation by Melissa officinalis L. ssp. officinalis in rat isolated thoracic aorta.

In the current study, vasorelaxant effect produced by the aqueous extract of Melissa officinalis L. ssp. officinalis (MOO) (Lamiaceae) and its possible mechanism in isolated rat aortic rings precontracted with phenylephrine were examined. In the first series of experiments, effect of MOO on the baseline and phenylephrine (10(-5)M) precontracted arteries was investigated, while in the second group of experiments, endothelium intact or endothelium denuded effect was determined. The agents used were N(omega)-nitro-L-arginine (L-NAME), an irreversible inhibitor of nitric oxide (NO) synthase, indomethacin (10 microM), a cyclooxygenase (COX) inhibitor, and glibenclamide (10 microM), an ATP-sensitive potassium channel blocker. The extract was found to exert a vasorelaxant effect and rosmarinic acid quantity, the characteristic compound of the plant, was analyzed by reversed-phase high-performance liquid chromatography (18.75%), and was further confirmed by LC-MS analysis giving a prominent [M(+1)] molecular ion peak at m/z 365. Total phenol amount in the extract was determined using Folin-Ciocalteau reagent (0.284 mg/mg extract). Vasorelaxant effect of the extract was entirely dependent on the presence of endothelium and was abolished by pretreatment with L-NAME, whereas pretreatment with indomethacin and glibenclamide reduced the relaxation to a minor extent. Rosmarinic acid was also tested in the same manner as the extract and was found to exert vasorelaxant effect. These results suggest that the aqueous extract of MOO vasodilates via nitric oxide pathway with the possible involvement of prostacycline and endothelium-derived hyperpolarizing factor (EDHF) pathways as well.

Effects of lidocaine on rabbit isolated thoracic aorta.

Lidocaine has been demonstrated to modify both contraction and relaxation of the vascular smooth muscle. Although lidocaine has been shown to inhibit endothelium-independent relaxations, the effects of lidocaine on arterial relaxation induced by peroxynitrite, a reaction product of superoxide and nitric oxide, have not been studied. The current study was designed to evaluate the effects of lidocaine on endothelium-dependent and -independent relaxations in isolated rabbit thoracic aorta. Rings of the rabbit thoracic aorta with or without endothelium were mounted for isometric force recording. Concentration-response curves to calcium ionophore A23187 ( 10(-9)to 3 x 10(-6)m), acetylcholine ( 10(-9)to 10(-3)m), sodium nitroprusside (SNP, 10(-9)to 10(-3)m), and peroxynitrite ( 10(-9)to 10(-3)m) were obtained in a cumulative manner. Lidocaine ( 10(-6)to 10(-4)m) was applied 15 min before addition of phenylephrine. Under resting force, lidocaine produced contractions at high concentrations ( 10(-5)to 10(-2)m) in endothelium-intact and -denuded arteries but removal of the endothelium did not significantly affect contractile activity. In phenylephrine-precontracted arteries, lidocaine caused concentration-dependent relaxations in both endothelium-intact and -denuded arteries. Inhibition of nitric oxide synthase or removal of endothelium did not affect the relaxations to lidocaine. Lidocaine suppressed the endothelium-independent relaxations of peroxynitrite, also poly (ADP-ribose) synthetase (PARS) enzyme activator, and SNP at high concentrations. Concentration-dependent vascular relaxations to A23187 and acetylcholine were significantly inhibited by lidocaine. These results suggest that lidocaine can depress vascular relaxations by a complex mechanism including inhibition of PARS enzyme activity.

Hypochlorous acid-induced responses in sheep isolated pulmonary artery rings.

The formation of reactive oxygen species (ROS) appears to play a significant role in many pathological states including cystic fibrosis and asthma. Although stimulated inflammatory cells represent a major source of oxygen metabolites and these cells are able to generate the potent oxidant hypochlorous acid (HOCl) effects of HOCl on arteries are not known. HOCl at low concentrations (10(-7)to 10(-4)m) did not affect the resting force or have an action in precontracted sheep pulmonary arteries. HOCl at 10(-4) m concentration reduced histamine-induced relaxations in endothelium intact preparations. However, at high concentrations (10(-2) to 1 m) HOCl led to constriction under resting conditions and caused vasodilation in endothelium intact and denuded serotonin (10 microm) precontracted arteries. These effects of HOCl were significantly reduced by pretreatment of l -arginine (10(-3)m), sodium nitroprusside (SNP, 10(-5) m) and N -acetyl-l-cysteine (NAC, 10(-4) m). The effects of SNP and NAC on HOCl-induced responses were due to direct interaction since only these compounds markedly diminished the HOCl-induced luminol chemiluminescence (CL). Lack of contraction with KCl after high concentrations of HOCl showed that HOCl causes irreversible tissue damage. These results suggest that HOCl produce vasoconstriction under resting force and cause vasodilation when the pulmonary arteries precontracted. HOCl may interact with endothelium-derived mediators and contribute to tissue injury and vascular dysfunction seen in disease states.