Subject(s)
Calcium/metabolism , Caspases/metabolism , Membrane Proteins/metabolism , Mutation/genetics , Neurons/drug effects , Neurotoxins/toxicity , Ryanodine Receptor Calcium Release Channel/metabolism , Amyloid beta-Peptides/pharmacology , Animals , Apoptosis/drug effects , Caspase 3 , Dantrolene/pharmacology , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/metabolism , Enzyme Activation/drug effects , Gene Expression Regulation , Genes, Transgenic, Suicide , Glutamic Acid/pharmacology , Membrane Proteins/genetics , Mice , Neurons/enzymology , Neurons/metabolism , Neurotoxins/pharmacology , PC12 Cells , Presenilin-2 , Protein Transport , RatsABSTRACT
Panax ginseng is well known to enhance the release of nitric oxide (NO) from endothelial cells of the rat aorta and to reduce blood pressure in animals. In this study, we investigated the effects of water extract of Korea red ginseng (KRG) on NO concentration levels in the exhaled breath, blood pressure, and heart rate of human volunteers. We also are interested in whether NO levels in exhaled breath are increased by KRG extract, and correlated with blood pressure and heart rate. Twelve healthy, non-smoking male volunteers were recruited for this study. A single administration of KRG water extract (500 mg/50 kg) increased NO levels in exhaled breath, and concomitantly decreased mean blood pressure and heart rate. The correlation value between NO levels and heart rate (r = 0.94), and the correlation value between NO levels and heart rate (r = 0.84) are significant (P < 0.01). Linear regression analysis shows the clear conversed correlation between NO levels and blood pressure as well as heart rate. Therefore, present data suggest that KRG may be useful for the treatment of hypertension and pulmonary vascular obstruction.
Subject(s)
Blood Pressure/drug effects , Heart Rate/drug effects , Nitric Oxide/biosynthesis , Panax/chemistry , Antihypertensive Agents/pharmacology , Breath Tests , Humans , Male , Medicine, East Asian Traditional , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Solutions/chemistry , Water/chemistryABSTRACT
This study was performed to investigate whether nitric oxide (NO) precursor (L-arginine), NO donor (S-nitroso-N-acetylpenicillamine, SNAP) and NO synthase inhibitors [N(G)-nitro-L-arginine-methylester (L-NAME) and N(G)-nitro-L-arginine (L-NOARG)] modulate morphine-induced anxiolytic effects in the plus-maze. L-Arginine (100, 200 and 300 mg kg(-1), i.p.) and SNAP (4, 8 and 10 mg kg(-1), i.p.) reduced the anxiolytic effect of morphine (20 mg kg(-1), s.c.). L-NAME (10, 20 and 40 mg/kg, i.p.) and L-NOARG (10, 15 and 20 mg kg(-1), i.p.) enhanced the anxiolytic effects of morphine (20 mg kg(-1), s.c.). On the other hand, L-arginine and SNAP increased the morphine-induced locomotor activity. L-NAME decreased the morphine-induced locomotor activity, but L-NOARG did not modify the morphine-induced locomotor activity. Therefore, these results suggest that the anxiolytic effects of morphine can be modulated by NO systems.
Subject(s)
Anti-Anxiety Agents/pharmacology , Morphine/pharmacology , Nitric Oxide/metabolism , Animals , Anti-Anxiety Agents/administration & dosage , Anti-Anxiety Agents/antagonists & inhibitors , Arginine/pharmacology , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Male , Maze Learning/drug effects , Mice , Mice, Inbred ICR , Morphine/administration & dosage , Morphine/antagonists & inhibitors , Motor Activity/drug effects , Motor Activity/physiology , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitroarginine/pharmacology , Receptors, N-Methyl-D-Aspartate/drug effects , S-Nitroso-N-Acetylpenicillamine/pharmacologyABSTRACT
This study was performed to investigate the effect of tetrahydroisoxazolopyridine (THIP), a GABAA agonist, on the morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity in mice. However, the morphine-induced hyperactivity was inhibited dose-dependently by the administration of THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of morphine resulted in a reverse tolerance to the hyperactivity caused by morphine (10 mg/kg, s.c.). THIP inhibited the development of reverse tolerance in the mice that had received the repeated same morphine (10 mg/kg, s.c.) doses. The postsynaptic dopamine receptor super-sensitivity, which was evidenced by the enhanced ambulatory activity after the administration of apomorphine (2 mg/kg, s.c.), also developed in the reverse tolerant mice. THIP also inhibited the development of the postsynaptic dopamine receptor supersensitivity induced by the chronic morphine administration. These results suggest that the hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited activating the GABAA receptors.
