Angiotensin II ; metabolism ; Cells, Cultured ; Endothelial Cells ; drug effects ; secretion ; Endothelins ; secretion ; Humans ; Polyphenols ; pharmacology ; Propanolamines ; pharmacology ; Tea ; chemistry ; Weightlessness Simulation

OBJECTIVETo investigate the role of endothelin (ET) in the proliferation and collagen synthesis of human scar-derived fibroblasts and the modulation of its antagonists such as nitric oxide (NO), tetrandrine (Tet).

METHODSWith the cultured fibroblasts from the scarring tissue, the cell proliferation was determined by [3H]-TdR incorporation, while the collagen synthesis was evaluated by [3H]-proline incorporation.

RESULTSThe ET-1 was significantly increasing the proliferation and collagen synthesis of human scar-derived fibroblasts. The values of [3H]-TdR absorption in the 2.5 ng/ml, 25 ng/ml and 100 ng/ml of ET-1 groups were 1.8 times, 4 times and 4.9 times more than in the control group, respectively (P < 0.01), while the values of the [3H]-proline incorporation were 1.1 times, 3.1 times and 3.8 times respectively (P < 0.01). The fibroblasts, treated with 50 micrograms/ml of S-nitroso-N-acetyl penicillamine(SNAP), were no detectable effect on the basal level of DNA synthesis, but produced decreasing effect on the [3H]-TdR absorption (the rate of inhibition was 22.89%, P < 0.05). It was found that the SNAP inhibited the [3H]-proline incorporation in cultured fibroblasts, but the rate of [3H]-proline incorporation induced by ET-1 was unaltered. The Tet with 3 micrograms/ml, in which does not inhibit the basal level of DNA synthesis, was significantly decreasing the collagen synthesis and decreasing the ET-mediated DNA synthesis (the rate of inhibition was 33.21% (P < 0.01).

CONCLUSIONThese results indicate that the ET can obviously increase the proliferation and collagen synthesis of human scar-derived fibroblasts, but it can be partially antagonized by NO and Tet.

Benzylisoquinolines ; pharmacology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cicatrix ; pathology ; Collagen ; biosynthesis ; DNA ; biosynthesis ; Endothelins ; antagonists & inhibitors ; pharmacology ; Fibroblasts ; cytology ; radiation effects ; Humans ; Nitric Oxide ; metabolism ; pharmacology ; Proline ; metabolism ; S-Nitroso-N-Acetylpenicillamine ; pharmacology

AIMTo investigate the effects of pravastatin on endothelin(ET) expression induced by aldosterone in cultured neonatal rat cardiac fibroblasts.

METHODSET concentration in conditioned medium was measured by radioimmunoassay, intracellular ET-1 level was evaluated by flow cytometry, and the expression of preproendothelin-1 (ppET-1) was detected and quantified using reverse transcriptase-polymerase chain reaction (RT-PCR) method.

RESULTSThe cardiac fibroblasts, treated with aldosterone at 107 mol/L, significantly up-regulated ppET-1 mRNA expression, as well as ET-1 synthesis and release. Pravastatin (10(-5), 10(-4), 10(-3) mol/L) dose-dependently blocked these effects. In contrast, pravastatin-induced inhibitory effects were reversed in the presence of mevalonate.

CONCLUSIONPravastatin down-regulated ppET-1 mRNA expression, as well as ET-1 synthesis and release induced by aldosterone in a process specifically related to mevalonate in cardiac fibroblasts.

Aldosterone ; metabolism ; Animals ; Cells, Cultured ; Endothelins ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Myoblasts, Cardiac ; drug effects ; metabolism ; Pravastatin ; pharmacology ; Rats ; Rats, Sprague-Dawley

Aldosterone ; pharmacology ; Animals ; Animals, Newborn ; Cells, Cultured ; Endothelins ; metabolism ; Myoblasts, Cardiac ; drug effects ; secretion ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the effect of pretreatment with captopril on myocardium ischemia-reperfusion injury in atherosclerotic rabbits. METHODS: Thirty-two New Zealand white rabbits were assigned randomly to the normally feed group, cholesterol-feed (CF) group, and cholesterol food plus captopril group (cap-feed group), which were fed for 10 weeks. We examined the changes in the size of the infarct and changes in the myocardium ultrastructure resulting from coronary ischemia/reperfusion. Levels of endothelin (ET) and nitic oxide (NO) were measured in the different experiment stages. RESULTS: The ET levels significantly increased and the content of NO significantly decreased in the CF group compared with those of the cap-feed group. The ultrastructure of myocardium cell was slightly destroyed and the infarct size was significantly smaller in the cap-feed group than the normally feed rabbits and CF rabbits. CONCLUSION The long-term captopril treatment can lighten the severity of myocardial injury produced by coronary ischemia/reperfusion.
Animals ; Captopril ; pharmacology ; therapeutic use ; Endothelins ; blood ; Male ; Myocardial Infarction ; blood ; drug therapy ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; ultrastructure ; Nitric Oxide ; blood ; Rabbits ; Random Allocation

OBJECTIVETo study the protective effects of saponines of stem and leaf of Panax notoginseng (PNSSL) on acute myocardial ischemia in anaesthetic dogs.

METHODThe acute ischemia models were made by ligation of left anterior descending (LAD) artery. The myocardial blood flow (MBF) was determined by ultrasonic doppler. The experiments adopted epicardiogram mapping to measure the scope and degree of myocardial ischemia, quantitative histologic assay (nitroblue tetrazolium, N-BT stain) to determine the size of myocardial infarction. And the endothelin (ET) and thromboxane B2 (TXB2) were measured by radioimmunological assay.

RESULTPNSSL was showed to obviously alleviate the degree of myocardial ischemia (sigma-ST) and narrow the ischemic area indicated by N-BT staining. In addition, PNSSL could increase the MBF of ischemia section. And the treatment could inhibit the ET and TXB2 release induced by ischemia and infarction.

CONCLUSIONPNSSL demonstrated to attenuate the damage subjected to myocardial ischemia and infarction, which may be due to its function of inhibiting the ET and TXA2 release, increasing the MBF, and then improving the damaged cardiac function.

Animals ; Coronary Circulation ; drug effects ; Dogs ; Endothelins ; blood ; Female ; Ginsenosides ; isolation & purification ; pharmacology ; Male ; Myocardial Infarction ; drug therapy ; physiopathology ; Panax ; chemistry ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry ; Protective Agents ; isolation & purification ; pharmacology ; Random Allocation ; Thromboxane B2 ; blood

OBJECTIVEDespite the causes for melanin increase, the increased gene expression of TYR is a common pathological process. Based on this viewpoint, antisense-S-Oligo of TYR was designed and synthesized to regulate synthesis of melanin in order to explore the treatment for skin pigmentation.

METHODSThe cultured melanocytes were divided into 3 groups. The group 1 was treated with endothelin, group 2 treated with ultraviolet ray and group 3 was used as the control. In each group, the 5' antisense-S-Oligo, the 3' antisense-S-Oligo, the mixed antisense-S-Oligo of TYR or Dotap only was added. The melanin content and TYR gene expressions were examined.

RESULTSThe 5' antisense-S-Oligo, the 3' antisense-S-Oligo and the mixed antisense-S-Oligo significantly inhibited the increase of melanin content and TYR gene expression, which were caused by endothelin or ultraviolet ray treatment. Of the three treatments, the 3' antisense-S-Oligo showed the strongest effect.

CONCLUSIONAntisense-S-Oligo has significant regulating effects on TYR gene expression and melanin content. The 3' antisense-S-Oligo is more effective than the 5' antisense-S-Oligo.

3' Flanking Region ; genetics ; 5' Flanking Region ; genetics ; Endothelins ; pharmacology ; Gene Expression ; Melanins ; biosynthesis ; Melanocytes ; drug effects ; metabolism ; radiation effects ; Oligodeoxyribonucleotides, Antisense ; genetics ; pharmacology ; Tyrosine ; genetics ; metabolism ; Ultraviolet Rays

AIMTo investigate the antagonistic effects of the novel compounds on vasoconstriction induced by ET-1 and the effect on the blood pressure of stroke-prone spontaneously hypertensive rats.

METHODSOrgan bath experiment and whole cardiac function experiment were used.

RESULTSThe analogues of o-CPhe-D-Trp-D-Phe(-X)-OH showed good ability against endothelin biological effects. When X was displaced by 3-F, 3-Cl or 4-Cl, the novel compounds inhibit the vascular constriction induced by ET-1 in a concentration-dependent manner, the IC50 +/- L95 were (0.09 +/- 0.05), (0.15 +/- 0.06) or (0.11 +/- 0.03) mumol.L-1 respectively. The blood pressure of stroke-prone spontaneously hypertensive rats was decreased. No significant effect on cardiac function of rats was discovered.

CONCLUSIONThe results demonstrate that among the six kinds of compounds, those with o-CPhe-D-Trp-D-Phe (-X)-OH configuration showed good biological effects.

Animals ; Aorta ; drug effects ; Blood Pressure ; drug effects ; Endothelin Receptor Antagonists ; Endothelins ; pharmacology ; Hypertension ; drug therapy ; physiopathology ; Male ; Molecular Structure ; Peptides ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Rats ; Rats, Inbred SHR ; Rats, Wistar ; Structure-Activity Relationship ; Vasoconstriction ; drug effects

OBJECTIVETo observe the variation of ET and CGRP contents in ischemic heart, and NO level in serum of myocardial damaged rats, and their regulation when with the protection of Xinshuping, a traditional Chinese medicine compound.

METHODThe models of myocardial ischemia were prepared by subcutaneous injection of isoproterenol or by ligation of coronary artery.

RESULTET content in myocardium was significantly increased (P < 0.01), and CGRP content as well as NO level in serum was not changed obviously in the model induced by isoproterenal. However, NO level in serum of rats treated with Xinshuping (ig bid x 2.5 d) was markedly raised (P < 0.01), neither ET not CGRP contents were affected by it. LDH and CK levels in serum of rats were evidently lowered by Xinshuping treatment. S-T segment's elevation of ECG was significantly inhibited and myocardial infarction size was reduced markedly by Xinshuping treatment in rats subjected to coronary artery ligature.

CONCLUSIONET, CGRP or NO is involved in myocardial infarction caused by isoproterenol. The ischemic damage or dysfunction in different models is obviously protected by Xinshuping. The promotion of NO release from vascular endothelium is probably related with this protective effect.

Animals ; Calcitonin Gene-Related Peptide ; metabolism ; Cardiotonic Agents ; pharmacology ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Endothelins ; metabolism ; Isoproterenol ; Male ; Myocardial Infarction ; chemically induced ; metabolism ; Myocardium ; metabolism ; Nitric Oxide ; blood ; Phytotherapy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the protective effect of verapamil pretreatment against cerebral ischemia-reperfusion injury in gerbils.

METHODSThirty-three Mongolian gerbils were randomized into the control group (group A, n=6, with sham operation), ischemia group (group B), and 3 verapamil groups (groups C, D, and E, n=7) with intraperitpneal verapamil injection (2 mg/kg) 48, 24 and 12 h before ischemia, respectively. In group A, the bilateral common carotid arteries were only exposed without clamping, and in the other 4 groups, the arteries were clamped for 20 min followed by reperfusion for 50 min. The gerbils were then decapitated and the forebrain cerebral cortex was removed to determine superoxide dismutase (SOD) and glutathione (GSH) activities and measure the contents of malondial dehyde (MDA), endothelin (ET) and calcitonin gene-related peptide (CGRP). The left forebrain cerebral cortex was sampled in each group to observe the ultrastructural changes under electron microscope.

RESULTSIn groups C and D, SOD activities were significantly higher than those in group B (P<0.05), and in group E, the SOD activity elevation was not statistically significant (P>0.05). In groups C, D and E, GSH activity was significantly higher than that in group B (P<0.05). MDA content was significantly lower in groups C and D than in group B (P<0.05), but comparable between groups E and B (P>0.05). ET content was also significantly lower in the pretreatment groups (P<0.05), but CGRP content higher (not statistically so, however) than those in group B. The more serious ultrastructural damage of the cerebral tissue was observed in group B, but only mild damage was found in the verapamil groups.

CONCLUSIONSVerapamil given 12-48 h before cerebral ischemia may protect the gerbils from cerebral ischemia-reperfusion injury by enhancing SOD, GSH activities and decreasing ET content.

Animals ; Brain ; drug effects ; metabolism ; pathology ; Brain Ischemia ; complications ; metabolism ; pathology ; prevention & control ; Endothelins ; metabolism ; Gerbillinae ; Glutathione ; metabolism ; Malondialdehyde ; metabolism ; Receptors, Calcitonin Gene-Related Peptide ; metabolism ; Reperfusion Injury ; complications ; metabolism ; pathology ; prevention & control ; Superoxide Dismutase ; metabolism ; Verapamil ; pharmacology