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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Baroreceptor sensitivity was studied in twelve young normotensive subjects and forty hypertensive patients, separated into two groups according to their age, severity of hypertension and signs of severe atherosclerotic vascular disease. Under stabilized circulatory conditions, the changes of pulse rate in response to changes of blood pressure, attained by infusion of trimethaphan camphorsulfonate alone or with norepinephrine, was examined. There was gradually diminished change of pulse rate in relationship to blood pressure change as age and hypertension advanced. However, although the blood pressure threshold of stimulation was obviously higher in the middle-aged hypertensive subjects than in the normotensive ones, the slightly reduced baroreceptor sensitivity was not significantly different from that in the normotensive group. Only in the elderly hypertensive patients was significantly diminished baroreceptor sensitivity demonstrated, which was also significantly different from that in the middleaged hypertensive patients. It is speculated that the significantly diminished baroreceptor sensitivity found in the elderly hypertensive patients may be due to atherosclerotic changes in the region of the baroreceptor, although proof of that is not available at the present time.
Atherosclerosis
PMID:Diminished baroreceptor sensitivity in elderly hypertensives. Possible role of atherosclerosis. 94 20

Sixty-one cases of thromboangitis obliterans (TAO) were studied during 1969-70. Nearly all were males, smokers, of poor socio-economic status. Average age of presentation was 34.2 years. A majority (64%) presented with claudication pain. About one fifth gave history of migratory thrombophlebitis and venography and histological investigations suggested that sixty per cent had venous involvement. Nearly half the patients had involvement of upper limb vessels. Clinical and arteriographic studies showed femoral-popliteal junction to be the commonest site of block. No evidence of coronary artery disease, cerebral vascular disease, abnormal glucose and lipid metabolism was seen in these patients. Arteriographic findings were unlike atherosclerosis obliterans (ASO). From this study we conclude that thromboangitis obliterans (TAO) is a separate and distinct clinical and pathologic entity and the incidence of venous involvement is very high if venographic investigations are combined with clinical examination.
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PMID:Thromboangitis obliterans: a clinical study with special emphasis on venous involvement. 105 73

The cellular events that occur in the vessel wall consequent to changes in endothelial permeability result in the progression of vascular disease, particularly atherosclerosis. Female rhesus monkeys were fed an atherogenic diet or were made hypertensive for 6-8 months; and their vessels were then compared with vessels from control monkeys. Length-defined segments of coronary vessels, the thoracic aorta, and the abdominal aorta showed significant increases in total connective tissue in the atherosclerotic and hypertensive groups; pulmonary vessels did not. The diseased aortic segments had increased levels of two lysosomal enzymes, acid phosphatase and beta-N-acetylglucosaminidase; pulmonary vessels were not diseased and did not show these changes. Coronary vessels from the atherosclerotic and hypertensive groups did not show an increase in enzyme levels on biochemical measurements, but focal accumulations of lysosomes were identified by cytochemical techniques. In atherosclerotic lesions, a doubling of cholesterol and more than a tenfold increase in cholesterol ester were found. These connective tissue and lysosomal changes are early features of primate vascular disease and may result from the accumulation of excessive substrate (cholesterol ester) in the lysosomes of vascular smooth muscle cells.
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PMID:Arterial lysosomes and connective tissue in primate atherosclerosis and hypertension. 111 47

A new strain of rat characterized by genetic obesity, endogenous hyperlipidemia, and hypertension was obtained in this laboratory. The abnormal phenotype is inherited as a homozygous recessive trait. The animals exhibit marked hypertriglyceridemia, moderate hypercholesterolemia, and an electrophoretic pattern resembling that of human Type IV hyperlipoproteinemia. The average life-span is less than 1 year, due largely to the development of premature renal and vascular disease. The kidney lesion has both glomerulonephritic and nephrosclerotic components and is accompanied by marked proteinuria. About 12% of animals develop urinary tract calculi. The vascular disease consists of fibrous and fatty-fibrous intimal plaques, and polyarteritis. The obese animal offers a useful model for investigating abnormal lipid metabolism and the etiology and pathogenesis of atherosclerosis.
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PMID:Pathologic findings and laboratory data in a new strain of obese hypertensive rats. 117 27

The morbidity and mortality in 172 males and 164 females with xanthomatosis have been investigated. Symptoms of coronary heart disease (CHD) were the most frequent initial manifestation of atherosclerotic vascular disease. Angina pectoris was the first symptom in about 3/4 of males as well as females; myocardial infarction was the first event in 26% of the males and 9% of the females. Other manifestations of atherosclerosis were comparatively rare and occurred late in life. Half of the subjects were affected with symptoms of atherosclerotic vascular disease by the age of 52 in men and 62 in women, the mean age for first symptoms being 49 and 56 years, respectively. No significant influence of other CHD risk factors than xanthomatosis and hyperlipidaemia was found in these patients. An increase in the number of cardiovascular deaths was seen in xanthomatosis patients, compared with the general population, in particular in the number of "sudden deaths". Half of the males died before the age of 66 and half of the females before the age of 74.5, which is about 10 and 7 years earlier than predicted at 30 years of age for the normal population. The cumulative relative mortality in both men and women was about twice that expected for the general Norwegian population until 70 years of age.
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PMID:The risk of atherosclerotic vascular disease in subjects with xanthomatosis. 118 82

A new strain of genetically obese rat recently obtained in our laboratory exhibits endogenous hyperlipidemia (marked hypertriglyceridemia and moderate hypercholesterolemia) and spontaneous hypertension. The animals die prematurely from kidney failure or from the complications of atherosclerosis. A low calorie diet proved to be highly beneficial to these rats. Body weight declined, obesity diminished, the hypertriglyceridemia was almost eliminated, and the hypercholesterolemia was reduced. However, the hypertensive state was not alleviated. Since the life span of the rats was greatly prolonged by a low calorie diet, the latter undoubtedly served to prevent or arrest the development of renal and vascular disease in these obese animals.
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PMID:Effect of low calorie diet on the hyperlipidemia, hypertension, and life span of genetically obese rats. 125 Aug 73

Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30-300 micrograms/ml), but not native low density lipoproteins (200 micrograms/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 micrograms/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endothelium evoked by Ox-LDLs. The Ox-LDL-stimulated production of the peptide was further augmented in the presence of thrombin (4 units/ml) and was unaffected by nitric oxide-generating compound 3-morpholinosydnonimine (10(-5) M). These results suggest that Ox-LDL may be an endogenous mediator of the augmented release of endothelin observed in hyperlipidemia and atherosclerosis. The increased production of the peptide could contribute to vasospastic events and may promote vascular smooth muscle proliferation and progression of atherosclerotic vascular disease.
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PMID:Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium. 131 34

Hypercholesterolemia and hypertension are two of the major risk factors associated with increased atherosclerotic vascular disease. An abnormal platelet function is one of the mechanisms proposed to participate in atherogenesis. This study was undertaken to find out whether hypercholesterolemia in hypertensive patients can change platelet lipid composition and reactivity. Twenty-nine untreated hypertensive patients were distributed into 3 age, body mass index and blood pressure-matched groups according to their plasma cholesterol levels (normal, borderline or elevated, group NC, BC and HC respectively). Their platelet lipid composition, cytosolic Ca2+ concentration, cyclic AMP content and aggregating response to ADP and collagen were determined. Platelet from group HC patients were characterized by reduced cyclic AMP content (evaluated in the presence and absence of a platelet phosphodiesterase inhibitor) and aggregating responses to ADP and collagen, increased palmitic acid content and decreased arachidonic, eicosapentaenoic and docosatetraenoic and pentaenoic acid content, resulting in a lowered polyunsaturated to saturated fatty acid ratio (P less than 0.001). In contrast, platelet cytosolic Ca2+ concentration, DPH steady-state anisotropy and cholesterol to phospholipid molar ratio were not significantly changed. This indicates that hypercholesterolemia is accompanied in hypertensive patients by marked changes in platelet fatty acid composition, cyclic AMP content and response to aggregating agents. These changes, which clearly differ from those induced by in vitro cholesterol loading, could reflect not only the balance between LDL and HDL stimulation but also an adaptation to hemodynamic perturbations.
Atherosclerosis 1992 Jun
PMID:Biochemical and functional alterations associated with hypercholesterolemia in platelets from hypertensive patients. 132 32

Endothelial cells produce the 21-amino acid peptide endothelin, which is formed from its precursor, big endothelin, via the activity of converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1, and hypoxia. In vascular smooth muscle, endothelin binds to a specific receptor (ETA-subtype), which activates phospholipase C, leads to the formation of inositol trisphosphate, diacylglycerol (which activates protein kinase C), and increased intracellular Ca2+. In certain blood vessels, the endothelin receptor on vascular smooth muscle is linked to a voltage-operated Ca2+ channel via a G-protein. This explains why Ca2+ antagonists inhibit endothelin-induced contractions in certain, but not all, blood vessels. In the human forearm circulation, Ca2+ antagonists do prevent endothelin-induced contractions and unmask endothelin-induced vasodilation mediated by endothelial prostacyclin production (via the ETB-receptor). The pulmonary circulation plays an important role in the metabolism of endothelin, as the lungs take up large quantities of the peptide during passage. Endothelin has profound vasoconstrictor effects in the pulmonary circulation (and also in bronchial tissue), and its production is augmented in pulmonary hypertension. In systemic hypertension, the circulating endothelin levels appear to be normal. In atherosclerosis and other forms of vascular disease, circulating endothelin levels are increased. Thus, endothelin is a potent mediator in the systemic and pulmonary circulation and, in particular, in diseases of the vasculature.
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PMID:Endothelin: systemic arterial and pulmonary effects of a new peptide with potent biologic properties. 133 60

We investigated whether biologically relevant concentrations of the mono-hydroxyeicosatetraenoic acids (mono-HETEs) modulate platelet functions. We report that 15-HETE, an eicosanoid produced by endothelial cells, granulocytes, and lymphocytes, potentiated platelet aggregation, nucleotide release, and elevation in intracellular calcium levels induced by a threshold concentration of thrombin (0.025 U/mL). Significant potentiation effects on these responses were observed at concentrations between 1 and 100 nmol/L. 15-HETE at these concentrations enhanced thrombin-induced platelet aggregation by 32% to 57%, nucleotide release by 40% to 65%, and elevation of intracellular calcium by 31% to 52% (P < .05 to .01). Both 12-HETE and 5-HETE, the structural isomers of 15-HETE, also potentiated thrombin-induced platelet aggregation and nucleotide release. While 12-HETE showed a small but significant effect at 100 pmol/L, 5-HETE had effects similar to those of 15-HETE at micromolar concentrations. To understand the mechanism of the HETE modulation of platelet functions, we studied the effect of 10 and 100 nmol/L 15-HETE on the production of sn-1,2-diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (1,4,5-IP3). 15-HETE enhanced thrombin-induced production of DAG and 1,4,5-IP3 in a time- and concentration-dependent manner. 15-HETE also potentiated agonist-induced phosphorylation of the 47-Kd platelet protein. These studies demonstrate an important modulatory role for 15-HETE on platelet functions. Since this eicosanoid is elevated in pathologic states associated with platelet hyperfunction, including diabetes mellitus and atherosclerosis, an elucidation of its mechanism(s) of action appears relevant to our understanding of the genesis of atherothrombotic vascular disease.
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PMID:15-Hydroxyeicosatetraenoic acid-mediated potentiation of thrombin-induced platelet functions occurs via enhanced production of phosphoinositide-derived second messengers--sn-1,2-diacylglycerol and inositol-1,4,5-trisphosphate. 133 1


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