Gene/Protein Disease Symptom Drug Enzyme Compound
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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

We compared the cardiovascular and renal actions of the neutral endopeptidase (NEP) inhibitor, SQ 28,603, in normal rats and in rats with healed myocardial infarcts. The infarcted rats were studied in the conscious state 8 weeks after ligation of the left main coronary artery and 4 h after placement of cardiovascular and renal catheters. Infarct size was 39 +/- 1.2% of left ventricle circumference; right ventricle and lung weight to body weight ratios were twice those of normal rats. These postmortem values were shown to be associated with elevated left ventricular end diastolic pressure and high plasma atrial natriuretic peptide (ANP) concentration in separate groups of rats. SQ 28,603 at 100 mumol/kg intravenously (i.v.) caused urine volume and sodium excretion to increase by 79 +/- 11 microliters/min and 8.2 +/- 1.4 microEq/min, respectively, 20 min after injection in infarcted rats; these changes were significantly greater than those in normal rats (12 +/- 5 microliters/min and 1.6 microEq/min, respectively). Thoracic venous pressure decreased by 1.9 +/- 0.4 mm Hg 80 min after SQ 28,603 in infarcted rats and by only 0.1 +/- 0.1 mm Hg in normal rats (p less than 0.05 vs. infarcted rats). SQ 28,603 had no effects on mean arterial pressure (MAP), cardiac output (CO), or glomerular filtration rate (GFR). The observation that NEP inhibition has more pronounced effects in animals with high ambient ANP level than in those with normal ANP is consistent with previous studies in a variety of animal models and supports the concept that NEP inhibition potentiates endogenous ANP.
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PMID:Heart failure augments the cardiovascular and renal effects of neutral endopeptidase inhibition in rats. 172 Aug 29

Head up and down tilts were used for manipulating the central blood volume in eight volunteers. During head-up tilt thoracic electrical impedance (TI) increased from 36.7 (33.9-52.1) ohm (mean and range) to 41.9 (36.9-59.2) ohm, heart rate from 60 (49-72) to 80 (65-90) beats min-1 (P < 0.05) and decreased again to 57 (48-67) beats min-1 accompanying a fall in mean arterial pressure from 86 (76-97) to 54 (41-79) mmHg and in cardiac output from 9.2 (5.9-12.1) to 6.9 (3.4-8.8) 1 min-1 (n = 7, P < 0.07). Central venous pressure did not change significantly. Pulmonary arterial mean, 6 (3-12) mmHg, and wedge pressures, 4 (1-9) mmHg, decreased to 4 (1-11) and 1 (0-7) mmHg, respectively, and mixed, 78 (77-79%), and central venous oxygen saturations, 72 (71-73)%, fell to 62 (46-75) and 54 (44-58)%, respectively (P < 0.05). Atrial natriuretic peptide (ANP) was determined from blood of the superior vena cava and pulmonary and brachial arteries. Pulmonary artery ANP, 18.4 (7.5-30.7) pmol l-1, was higher than in vena cava, 13.3 (5.2-20.9) pmol l-1 (P < 0.05). At the time of presyncope, pulmonary artery ANP decreased from 20.8 (37.4-10.1) to 13.7 (19.7-5.7) pmol l-1, in vena cava from 13.8 (23.1-7.1) to 10.2 (17.9-6.7) pmol l-1 and in the brachial artery from 16.9 (34.1-5.2) to 11.3 (18.5-5.1) pmol l-1 (P < 0.05). Head-down tilt did not affect the recorded variables significantly. Thoracic electrical impedance, pulmonary artery pressure and venous oxygen saturations were sensitive indices of the central blood volume as reflected in the release of atrial natriuretic peptide from the right side of the heart.
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PMID:Thoracic impedance and pulmonary atrial natriuretic peptide during head-up tilt induced hypovolaemic shock in humans. 803 13

A domestic shorthaired cat was presented with a 1-month history of cardiomegaly and recurrent chylothorax. The heart rate was 130 beats/min and no P waves were present on a surface electrocardiogram. Thoracic radiographs and an echocardiogram demonstrated severe biatrial dilatation, pleural effusion and restrictive pleural disease. Permanent atrial standstill was suspected. Pleurocentesis was performed and therapy was started with enalapril, frusemide and aspirin. Intracardiac electrograms revealed no atrial activity, and atrial pacing failed to elicit atrial or ventricular depolarisations. The patient was euthanased. Necropsy showed severe atrial wall thinning with marked cardiocyte loss. Persistent atrial standstill is a rare disease in the cat. Clinical signs may have been due to loss of atrial function, ventricular diastolic dysfunction, bradycardia, neurohormonal activation and reduced atrial natriuretic peptide plasma concentrations.
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PMID:Persistent atrial standstill in a cat. 1056 91

NO, constitutively produced by endothelial NO synthase (eNOS), plays a key regulatory role in vascular wall homeostasis. We generated transgenic (Tg) mice overexpressing eNOS in the endothelium and reported the presence of reduced NO-elicited relaxation. The purpose of this study was to clarify mechanisms of the reduced response to NO-mediated vasodilators in eNOS-Tg mice. Thoracic aortas of Tg and control mice were surgically isolated for vasomotor studies. Relaxations to acetylcholine and sodium nitroprusside were significantly reduced in Tg vessels compared with control vessels. Relaxations to atrial natriuretic peptide and 8-bromo-cGMP were also significantly reduced in Tg vessels. Reduced relaxations to these agents were restored by chronic N(G)-nitro-L-arginine methyl ester treatment. Basal cGMP levels of aortas were higher in Tg mice than in control mice, whereas soluble guanylate cyclase (sGC) activity in Tg vessels was approximately 50% of the activity in control vessels. Moreover, cGMP-dependent protein kinase (PKG) protein levels and PKG enzyme activity were decreased in Tg vessels. These observations indicate that chronic overexpression of eNOS in the endothelium resulted in resistance to the NO/cGMP-mediated vasodilators and that at least 2 distinct mechanisms might be involved: one is reduced sGC activity, and the other is a decrease in PKG protein levels. We reported for the first time that increased NO release from the endothelium reduces sGC and PKG activity in mice. These data may provide a new insight into the mechanisms of nitrate tolerance and cross tolerance to nitrovasodilators.
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PMID:Mechanisms of reduced nitric oxide/cGMP-mediated vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase. 1090 19