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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin (5-hydroxytryptamine, 5HT) is believed to play a role in vasospasm and increased platelet aggregability that in turn could contribute to atherosclerosis. The present study was designed to evaluate a possible participation of serotonin in the development of vascular complications in diabetes mellitus. Whole blood and plasma serotonin, the platelet uptake and release of the amine and serotonin- induced platelet aggregation were studied in 32 patients with Type 2 diabetes. The patients were divided into three groups according to the presence and advancement of retinopathy. Mean levels of blood serotonin content were significantly lower in diabetic patients. The concentration of the amine in the plasma was markedly increased in diabetes. It was correlated with vascular changes of the retina. We established that platelets from diabetic patients took up less serotonin when compared to the control group. Concomitantly enhanced spontaneous release of 5HT from platelets was observed. The platelets of diabetic patients showed increased response to serotonin. There was a relation between serotonin-induced aggregation and the presence of retinopathy. These results suggest that serotonin may be involved in the pathogenesis of diabetic vasculopathy.
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PMID:Blood serotonergic mechanisms in type 2 (non-insulin-dependent) diabetes mellitus. 151 34

Ketanserin, an S2 antagonist, has been shown to be an effective antihypertensive drug. Carefully controlled clinical trials have demonstrated that ketanserin is as effective as both metoprolol and thiaside diuretics in reducing blood pressure. However, unlike the beta-blocking drug metoprolol and the diuretics, the response rate to ketanserin is significantly greater in older patients, reflecting perhaps the greater vasoconstrictor effects of 5-hydroxytryptamine in patients with atherosclerotic disease. This enhanced vasoconstrictor response to serotonin in elderly patients may be matched by an increased effect on platelet aggregation, which is also blocked by ketanserin. There is very suggestive evidence from the PACK study that ketanserin may reduce vascular thrombotic episodes in patients with extensive atherosclerosis. This unique characteristic, combined with effectiveness as an antihypertensive agent, makes ketanserin a particularly useful drug in the treatment of elderly patients with hypertension and vascular disease.
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PMID:Age-related effects of 5-HT2 antagonists. 171 70

The endothelial cells can release both relaxing and contracting substances. The former include prostacyclin and endothelium-derived relaxing factor (EDRF, which most likely is nitric oxide, or a nitrosoderivative releasing nitric oxide, derived from L-arginine). Candidates as endothelium-derived contracting factors (EDCF) include superoxide anions thromboxane A2 and the peptide endothelin. Endothelium-derived relaxing factor causes relaxation of vascular smooth muscle by activation of the soluble form of guanylate cyclase which leads to an accumulation of cyclic GMP; it also reduces platelet adhesion and aggregation. The latter effect is synergistic with the inhibition evoked by prostacyclin. The release of EDRF and prostacyclin plays a key role in the protective role of the endothelium against vasospasm and the unwanted coagulation of blood. Indeed, thrombin and aggregating platelets are potent stimuli for the release of EDRF. The platelet-products responsible are the adenine nucleotides, ADP and ATP, which activate P2y-purinergic receptors on the endothelial cells and 5-hydroxytryptamine (serotonin) that stimulates 5-HT1-like serotonergic receptors. The response to serotonin, but not that to the adenine nucleotides, is mediated by a pertussis toxin-sensitive mechanism. When endothelial cells regenerate, or are cultured, they selectively lose the pertussis toxin-sensitive mechanism of release, which results in a marked decrease in sensitivity to exogenous and platelet-released serotonin. As a consequence, the endothelial cells exhibit a considerably reduced response to aggregating platelets. This phenomenon, which can be exacerbated by hypercholesterolemia, favors ongoing platelet aggregation and vasospasm, and constitutes a first step toward atherosclerosis.
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PMID:Platelet-derived serotonin, the endothelium, and cardiovascular disease. 171 75

We studied the morphological and contractile characteristics of rat thoracic aortic segments perfused for 3 or 6 days under pulsatile conditions. Light microscopic examination of the segments revealed the presence of an unchanged tunica media. However, the intimal surface was mostly devoid of endothelial cells. The perfused aortic segments showed a dramatic increase in spontaneous tone when compared to fresh and sham-treated aortic segments. Maximum responses to potassium and norepinephrine were reduced after 3 days of perfusion (20-40% reduction), while maximum responses to 5-hydroxytryptamine and angiotensin II were not significantly different. After 6 days of perfusion, maximum responses to all agonist were reduced (50-60%). Sensitivity to norepinephrine was not affected by the treatment, while sensitivity to 5-hydroxytryptamine was reduced. The perfused aortic segments relaxed well in response to isoproterenol. Our system provides a useful experimental model for short-term studies of hypertension- and atherosclerosis-related vascular changes. Further refinement and characterization could improve the performance of the system for longer-term studies.
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PMID:Morphological and contractile characteristics of rat aortae perfused for 3 or 6 days in vitro. 173 86

We have investigated the growth promoting activities of two potent vasoactive substances, serotonin and angiotensin II (AII), on cultured porcine aortic smooth muscle cells (ASMC), using a defined serum-free medium. Serotonin (30 nM to 30 microM) stimulated ASMC DNA synthesis both alone and in combination with platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). Serotonin-induced DNA synthesis was significantly inhibited by ketanserin (5-hydroxytryptamine-2 (5HT-2) receptor antagonist). AII (3-10 nM) failed to stimulate ASMC DNA synthesis directly, either alone or in combination with PDGF or EGF. Since both serotonin and AII were found to activate phosphatidylinositol turnover and are reported to mobilise intracellular calcium, it is apparent that these events alone are insufficient to stimulate ASMC mitogenesis.
Atherosclerosis 1991 Jun
PMID:Comparison of the mitogenic activity of angiotensin II and serotonin on porcine arterial smooth muscle cells. 189 86

In the present study we used a new model, in which the positioning of a non-occlusive collar around the rabbit carotid artery results, within 7 days, in the generation of a neo-intima, a precursor lesion of atherosclerosis. We investigated the effects of this intimal proliferation on the responsiveness to serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NOR) after 1, 2 and 7 days. Already after 1 day the collar-treated arteries were more sensitive to 5-HT, but not to NOR. This sensitivity persisted over a period of 7 days. However, the development of a neo-intima diminished the maximum contractile force to NOR after 2 and 7 days, but not to 5-HT. These results demonstrate that there is a relatively selective increase in sensitivity to 5-HT during neo-intima formation, even without hyper-cholesterolaemia.
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PMID:The effect of a developing neo-intima on serotonergic and adrenergic contractions. 207 25

A survey shall be given on the physiological, pathophysiological and pharmacotherapeutic backgrounds of the biogenic amine 5-hydroxytryptamine (serotonin; 5HT), to be preceded by a few historical remarks. 5HT is biosynthesized from L-tryptophan via hydroxylation and subsequent decarboxylation. 5HT is predominantly found in enterochromaffin cells, platelets and in various structures of the central nervous system. Its concentration in circulating blood is low and probably subthreshold. Whereas the physiological role of 5HT is rather unclear, 5HT appears to play a relevant role in certain psychiatric disorders, in migraine and the carcinoid syndrome. Its role in essential hypertension remains uncertain. However, 5HT appears to contribute to and to exacerbate the damage to blood vessels which were already predamaged by atherosclerosis, diabetes mellitus or possibly old age as such. A major breakthrough in the pharmacology of the serotonergic system was achieved by the discovery of several subtypes of 5HT receptors, with a corresponding collection of selective agonists and antagonists towards these receptor subtypes. This development is the basis of various drugs which interact with the serotonergic system and its receptors, like the various 5HT2 receptor antagonists (of which ketanserin is the prototype), methysergide, pizotifen, urapidil, flesinoxan and a variety of psychoactive drugs. The most important of these drugs and their potential application will be discussed with an emphasis on cardiovascular disorders.
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PMID:Pathophysiological and pharmacotherapeutic aspects of serotonin and serotonergic drugs. 213 70

Serotonin is a widely distributed amine, although 95% is found in the enterochromaffin cells of the gastrointestinal mucosa. Its effects are mediated via a large number of receptors differing in their physiological and pharmacological properties. Its principal actions are on the cardiovascular system, both directly and potentiating the effects of the vasoconstriction from noradrenaline, angiotensin and histamine; similarly it potentiates the effect of various platelet aggregating substances. There is evidence that 5-hydroxytryptamine releases endothelium-derived relaxing factor attenuating its direct constriction effect and in the human forearm an increase in flow is seen from serotonin. In the absence of endothelium as in atherosclerosis, vasoconstriction occurs. Serotonin antagonism may have useful therapeutic effects and ketanserin has undergone wide evaluation. There is evidence that ketanserin should be avoided with potassium-losing diuretics as an increased mortality has been reported with the combination.
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PMID:Serotonin: receptors and antagonists--summary of symposium. 213 73

Platelet activation releases thromboxane A2 and serotonin, which acts on blood vessels through a specific, 5-hydroxytryptamine (5-HT2) receptor. The development of ketanserin, the selective 5HT2 receptor blocker, has made it possible to explore the role of serotonin in patients with advanced atherosclerotic disease. Ketanserin in low doses (3 to 30 micrograms/kg) was administered intra-arterially to 23 patients with symptomatic peripheral occlusive vascular disease during peripheral angiography: an additional seven patients received a placebo. The angiographic response was evaluated by coded reading and by computer-assisted measurement of arterial segments in four anatomical regions (pelvis, thigh, knee, and lower leg). Hemodynamic changes were assessed by mercury strain gauge plethysmography and Doppler pressure measurement. Unequivocal vasodilatation was observed in zero of seven placebo-treated patients and in 13 of 23 (57%) treated patients primarily at the level of collateral vessels. Dilation of the geniculate arteries, a major source of collaterals to the calf, was associated with a significant increase in the blood flow delivery to the calf. There was a moderate drop of systemic blood pressure in patients who failed to respond with peripheral vasodilatation. Ketanserin induces hemodynamically significant vasodilatation in some patients with peripheral vascular disease, suggesting that serotonin may contribute to ischemia in some patients with advanced atherosclerosis.
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PMID:Atherosclerosis, peripheral arterial disease and the vascular response to ketanserin. 234 79

The direct vasoactive effects of native and oxidatively modified low density lipoproteins as well as their effects on endothelium-dependent relaxations to 5-hydroxytryptamine were studied in isolated rings of pig right coronary artery. Slowly developing contractions were caused by native low density lipoproteins (100 micrograms protein/ml). The contractions were more pronounced in the absence than in the presence of the trace metal chelator, EDTA, and coincided with the formation of lipid peroxides during the response. The lipophilic antioxidant, butylated hydroxytoluene, prevented the oxidation of, and contraction to, native low density lipoproteins. Low density lipoproteins oxidized by exposure to copper contracted coronary arteries more rapidly with a threshold of only 1 micrograms protein/ml, but with a similar maximal contraction at 100 micrograms protein/ml. Superoxide dismutase inhibited the contraction to native low density lipoproteins, but not to oxidized low density lipoproteins. Catalase blocked contractions to both native and oxidized low density lipoproteins. Contractions to oxidized low density lipoproteins were unaffected by indomethacin, but were abolished by removal of the endothelium or by inhibitors of endothelium-derived relaxing factor. Oxidized low density lipoproteins but not native low density lipoproteins inhibited endothelium-dependent relaxations to 5-hydroxytryptamine. Thus, oxidized low density lipoproteins caused endothelium-dependent coronary artery contractions which are mediated by a hydroperoxide. Contractions to native low density lipoproteins are due to their oxidation in the organ chamber by the superoxide anion radical. Oxidized, but not native, low density lipoproteins impair normal endothelial cell vasodilator function in vitro. Oxidized low density lipoproteins, important in the pathogenesis of atherosclerosis, may directly contribute to the increased risk of vasospasm seen in hypercholesterolemia and atherosclerosis.
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PMID:Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery. 236 28


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