UMLS:C0729233 - FACTA Search

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Query: UMLS:C0729233 (Thoracic)
6,478 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to examine the alterations in vascular relaxation responsiveness to endothelium-dependent or -independent vasodilators, including atrial natriuretic peptide (ANP) and acetylcholine, in aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits during the progression of the atherosclerotic plaque. WHHL rabbits were divided into two groups according to age: group 1, 6-11 months, and group 2, 12-18 months. The isolated thoracic aortas obtained from both normal (control) and WHHL rabbits were suspended in a bath containing oxygenated Krebs' buffer for recording of isometric force. The endothelium-dependent relaxation evoked by acetylcholine was reduced in group 1 WHHL rabbits and decreased progressively in proportion to the degree of atherosclerosis progression when compared with age-matched control rabbits. ANP-induced relaxation was not significantly decreased in group 1 WHHL rabbits. However, ANP-induced relaxation was markedly impaired in group 2 WHHL rabbits. Thoracic aortas with severe atherosclerosis were less sensitive to ANP, with a significant increase in the median effective dose, although maximum relaxation induced by ANP was not reduced. Accumulation of cyclic GMP induced by ANP and acetylcholine was markedly reduced in atherosclerotic arteries obtained from group 2 WHHL rabbits compared with control rabbits. Vascular relaxation elicited by nitroglycerin or isoproterenol was not significantly impaired in atherosclerotic arteries from either group 1 or group 2 WHHL rabbits. From these results, we suggest that ANP-induced cyclic GMP formation and vascular relaxation via particulate guanylate cyclase in vascular smooth muscle cells are impaired in severely atherosclerotic arteries.
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PMID:Impaired vasodilatory response to atrial natriuretic peptide during atherosclerosis progression. 131 25

SIN1 (the active metabolite of molsidomine), nitroglycerin, and endothelium-derived relaxing factor (EDRF) produce vasodilation by activation of soluble guanylate cyclase. Therefore, prolonged exposure to SIN1 might affect not only the responses to SIN1 itself and to nitroglycerin but also to EDRF. In vivo treatment of rats consisted of subcutaneous injections of either SIN1 (60 mg/kg) for the treated group or placebo for the control group, twice daily for 3 days. Thoracic aortas from the treated group were threefold and sixfold less sensitive to nitroglycerin and SIN1, respectively. The endothelium-dependent relaxations to acetylcholine were, nevertheless, similar in both groups. Moreover, the concentration-response curves to phenylephrine, which are known to be modulated by the endothelium, were similar in both groups. In addition, incubation with methylene blue (10 microM for 30 min), which blocks the vasodilator action of EDRF, potentiated in the same way the contractions to this alpha-adrenergic agonist. The increase in resting tone induced by methylene blue incubation was also equivalent in the two groups. The present results show that SIN1 treatment for several days in rats is associated with slight tolerance development not only to SIN1 itself but also to nitroglycerin, while the endothelial function remains operative. We conclude that the mechanisms involved in the activation of guanylate cyclase by SIN1 and nitroglycerin are probably different than those of EDRF-mediated responses.
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PMID:Effects of in vivo SIN1 treatment on nitrovasodilator relaxation and on EDRF-mediated responses in rat aorta. 170 6

Vascular relaxation by the organic (nitroglycerin) and inorganic (sodium nitroprusside) nitrovasodilators and the endothelium-dependent vasodilators (acetylcholine and histamine) has been associated with cyclic GMP accumulation. Tolerance to vasodilation by nitroglycerin commonly occurs following prolonged exposure to nitroglycerin. This study investigates the effects of in vivo nitroglycerin therapy on vascular relaxation and cyclic GMP accumulation induced by the nitrovasodilators and the endothelium-dependent vasodilators. Rats were injected with nitroglycerin or the propylene glycol diluent control for 4-7 days. Thoracic aortas from the nitroglycerin-treated rats were 750-fold less sensitive to the relaxant effects of nitroglycerin. In contrast, these aortas were only threefold less sensitive to the relaxant effects of sodium nitroprusside, while the maximum relaxation to acetylcholine and histamine was depressed by 50 and 41%, respectively. Desensitization to relaxation was associated with reduced cyclic GMP elevations to all the vasodilators. Relaxation to 8-bromo cyclic GMP, dibutyryl cyclic AMP, or diltiazem was unaffected by nitroglycerin therapy. Tolerance was also associated with an increased sensitivity to the contractile effects of low concentrations of norepinephrine. This increased sensitivity to norepinephrine was associated with a decrease in cyclic GMP levels. The present results suggest that: (1) desensitization to nitroglycerin, sodium nitroprusside, acetylcholine, and histamine by nitroglycerin therapy may be at the level of cyclic GMP accumulation; (2) cyclic GMP is the common mediator of relaxation induced by the nitro- and endothelium-dependent vasodilators; (3) the mechanisms involved in the activation of guanylate cyclase and relaxation by sodium nitroprusside, acetylcholine, and histamine are probably different than those of nitroglycerin; and (4) cyclic GMP may be acting as a physiological negative feedback signal in agonist-induced contraction.
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PMID:Effect of in vivo nitroglycerin therapy on endothelium-dependent and independent vascular relaxation and cyclic GMP accumulation in rat aorta. 244 89

Thoracic electromaps were recorded before and after sublingual nitroglycerin (NG) in 26 subjects 15 and 30 days after acute myocardial infarction (MI), in order to evaluate the effect of the drug on injury potentials. Ten patients with documented left ventricular aneurysm were also studied 5 to 46 months after acute MI. Fifteen min after NG there was a significant decrease, compared with basal values, of ST segment elevations, blood pressure and rate-pressure product on both the 15th and 30th days. The degree of ST potentials reduction was not strictly related to the decrease of myocardial oxygen consumption, as indicated by the rate-pressure product. The response to NG on the 15th day did not predict accurately the evolution of injury potentials. In fact there was no significant correlation between percentages reduction of ST after NG on the 15th day and amplitudes of ST segment elevations present on the 30th day. In the patients with ventricular aneurysm, ST potential decrease and hemodynamic changes after NG were similar to those observed in the other groups studied. Our data suggest that it is not possible to differentiate between ST segment elevations associated with a dyssynergic area and those merely due to ischemic injury on the basis of NG sensitivity, and that ST segment elevations in the acute and subacute phase and long after MI have, at least in part, a similar electrophysiological significance.
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PMID:Effect of nitroglycerin on ST potentials in the post-acute phase of myocardial infarction. 679 90

Diabetes is known to cause impaired endothelium-dependent relaxation of blood vessels. The purpose of this study was to determine whether this endothelial dysfunction is a permanent defect or is reversible after acute arginine supplementation in vitro or by surgical intervention in vivo using syngeneic pancreatic islet transplantation. Lewis rats were injected with streptozotocin to induce diabetes and were studied either 8 or 12 weeks later. Another group received syngeneic islets via intraportal injection at 8 weeks of diabetes and were allowed to become euglycemic for 4 weeks before study. Thoracic aortic rings were tethered in isolated muscle baths, contracted with a submaximal concentration of norepinephrine, and challenged with either the endothelium-dependent vasodilator acetylcholine or the endothelium-independent vasodilator nitroglycerin. Relaxation to acetylcholine (but not nitroglycerin) was reduced in both 8- and 12-week diabetic rings compared with age-matched control rings. Preincubation of diabetic rings in vitro with L-arginine (but not D-arginine) restored relaxation to acetylcholine to normal to rings from 8-week but not 12-week diabetic animals. Plasma basic amino acids (arginine, lysine, and histidine) were reduced by diabetes, whereas other neutral or acidic amino acids were unchanged (phenylalanine, proline, and glutamate), reduced (serine, cysteine, threonine, tyrosine, tryptophan, and aspartate), or elevated (isoleucine, leucine, and valine). Islet transplantation restored to normal the changes in plasma amino acids. Elevation in blood glucose and total glycosylated hemoglobin in diabetic animals was normalized after islet transplantation. Furthermore, islet transplantation completely restored the defective endothelium-dependent relaxation to acetylcholine in diabetic rings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Syngeneic pancreatic islet transplantation reverses endothelial dysfunction in experimental diabetes. 765 36

We tested the hypothesis as to whether elevated arterial pressure in hypertension alters cGMP, or cAMP, mediated vasorelaxation. Relaxation to nitroglycerin and isoproterenol was determined in isolated aortic rings from one-kidney, one clip hypertensive (1K1C), coarctation hypertensive (CH) and normotensive control (C) rats. Thoracic aortas from 1K1C and CH rats, as well as abdominal aortas from 1K1C rats, but not abdominal aortas from CH rats were exposed chronically (4-6 weeks) to elevated arterial pressure. Sensitivity of rings with and without endothelium to nitroglycerin was suppressed significantly only in vessels exposed chronically to high arterial pressure. Impaired sensitivity to nitroglycerin in abdominal rings from 1K1C rats could not be abolished by exposure to 100 uM L-arginine, the substrate for production of NO by endothelial nitric oxide synthase, or 100 uM L-cysteine, the source of thiol groups required for the production of nitric oxide from nitroglycerin. Maximum relaxation to isoproterenol was impaired significantly in thoracic and abdominal rings, with and without endothelium, from 1K1C and CH rats. Relaxation to 8-bromo-cGMP and dibutyryl cAMP was similar in abdominal rings from all groups. We conclude that impaired vasorelaxation to nitroglycerin and isoproterenol in hypertension involves mechanisms prior to activation of vascular smooth muscle cGMP-dependent and cAMP-dependent protein kinase, respectively. Impaired cGMP, but not cAMP, mediated relaxation of aortas appears to result from their exposure to high arterial pressure per se. This effect does not appear to involve the vascular endothelium or vascular sources of thiols, but rather may reflect an effect of high arterial pressure to impair the ability of the artery to respond to nitric oxide derived from nitroglycerin.
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PMID:Selective effect of high arterial pressure in hypertension upon inhibition of cGMP versus cAMP mediated vascular relaxation. 884 63

Oxygen-derived free radicals are believed to be involved in diabetes-induced vascular complications. The role of oxygen radicals in endothelial dysfunction in diabetes is not known with certainty. In this study we tested whether inhibition of lipid peroxidation using the potent inhibitor U74389F, a 21-aminosteroid also known as lazaroid, could prevent endothelial dysfunction in diabetes. Lewis strain rats were made diabetic by intravenous injection of streptozotocin. A subgroup of diabetic animals received daily oral doses of 10 mg/kg U74389F at 72 hours post streptozotocin and throughout the 8-week duration of diabetes. Thoracic aortas were isolated and suspended in isolated tissue baths and contracted with norepinephrine. Relaxation due to the endothelium-dependent vasodilator, acetylcholine, was impaired in diabetic aorta while relaxation due to A23187 and nitroglycerin was unaltered. Chronic treatment of diabetic animals with U74389F normalized the increase in plasma lipid peroxides as assessed by thiobarbituric acid-reactive substances but did not alter serum insulin levels, blood glucose concentration, nor total glycosylated hemoglobin. Increases in aortic catalase activity resulting from diabetes was not altered by U74389F. Despite reductions in lipid peroxides, U74389F did not prevent the diabetes-induced impairment in endothelium-dependent relaxation caused by acetylcholine. These data suggest that other pathways that are antecedent to lipid peroxidation may be responsible for endothelial dysfunction in diabetes.
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PMID:Chronic treatment with the 21-aminosteroid U74389F, an inhibitor of lipid peroxidation, does not prevent diabetic endothelial dysfunction. 931 Feb 71

Endothelial cells play an important role in the regulation of vascular activity through the release of endothelium derived relaxing factor (EDRF) now believed to be nitric oxide (NO). NO and the NO donor drug nitroglycerin relax vascular smooth muscle by stimulating soluble guanylyl cyclase leading to elevation of intracellular levels of cyclic guanosine 3',5'-monophosphate (cGMP). Halothane has been shown to inhibit the action of NO on blood vessels. This study was designed to further investigate the mechanisms by which halothane attenuates NO-induced vascular relaxations. This was done by examining the effects of halothane on nitroglycerin and NO-induced relaxations in the presence and absence of the inhibitors of soluble guanylyl cyclase, methylene blue and 6-anilino-5,8-quinolinedione (LY 83583). Thoracic aortas from anesthetized male Sprague-Dawley rats were excised and cut into rings and the endothelium was removed. The aortic rings were suspended in organ baths containing Krebs solution and equilibrated at their optimal passive tension. When a stable plateau of contraction was produced by EC60 concentrations of norepinephrine, increasing concentrations of nitroglycerin or NO were added to the baths to relax the rings. This contraction-relaxation procedure was repeated three or four times. In some baths halothane was administered by a calibrated vaporizer 10 min before beginning the second procedure. Either methylene blue or LY 83583 was added to the baths 20 min before the third procedure. The combination of halothane, methylene blue or LY 83583 was added before the fourth procedure. Halothane, methylene blue or LY 83583 significantly inhibited nitroglycerin-induced relaxation individually. Halothane and LY 83583 also significantly inhibited NO-induced relaxations (5 x 10(-9)-3 x 10(-8) M and 5 x 10(-9)-3 x 10(-5) M, respectively) individually. The combination of halothane and methylene blue or halothane and LY 83583 significantly inhibited nitroglycerin-induced relaxation, also, the combination of halothane and LY 83583 significantly inhibited NO-induced relaxations. Halothane, methylene blue and LY 83583 treatment led to rightward shift in the concentration-effect curves. Halothane, in combination with methylene blue or LY 83583, produced inhibition equivalent to the sum of their individual effects. The present study demonstrates that the halothane, methylene blue and LY 83583 attenuate nitroglycerin and NO-induced relaxations of endothelium-denuded rat aortic rings. This suggests that halothane, methylene blue and LY 83583 may act through competitive antagonism at a common site of action on soluble guanylyl cyclase in the EDRF/NO relaxation pathway.
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PMID:Halothane attenuates nitric oxide relaxation of rat aortas by competition for the nitric oxide receptor site on soluble guanylyl cyclase. 954 89

Studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism underlying observed adverse vascular effects. Advanced age is one factor known to decrease antioxidant defenses and confer susceptibility to the detrimental vascular effects seen following PM exposure. The present study was designed to investigate the vasomotor responses following ultrafine PM exposure in wild type (WT) and superoxide dismutase 2-deficient (SOD2^+/-) mice that possess decreased antioxidant defense. Thoracic aortic rings isolated from young and aged WT and SOD2^+/- mice were exposed to ultrafine PM in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with rising amounts of nitroglycerin (NTG). Data demonstrated that ultrafine PM decreased the relaxation response in both young WT and young SOD2^+/- mouse aortas, and relaxation was significantly reduced in young SOD2^+/- compared to WT mice. Ultrafine PM significantly diminished the NTG-induced relaxation response in aged compared to young mouse aortas. After ultrafine PM exposure, the relaxation response did not differ markedly between aged WT and aged SOD2^+/- mice. Data demonstrated that the greater vascular effect in aortic rings in aged mice ex vivo after ultrafine PM exposure may be attributed to ultrafine PM-induced oxidative stress and loss of antioxidant defenses in aged vascular tissue. Consistent with this conclusion is the attenuation of NTG-induced relaxation response in young SOD2^+/- mice.
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PMID:Ultrafine particulate matter exposure impairs vasorelaxant response in superoxide dismutase 2-deficient murine aortic rings. 2927 24