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

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

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

Whole blood serum (WBS) rapidly induced the phospholipase C-mediated hydrolysis of phosphoinositides and subsequently stimulated DNA synthesis in cultured rabbit vascular smooth muscle cells (VSMCs). Ketanserin, a serotonin (S2) receptor antagonist, markedly inhibited the WBS-induced phospholipase C reaction and DNA synthesis. Serotonin by itself had a weak mitogenic activity for VSMCs, but this vasoconstrictor markedly stimulated the platelet-derived growth factor- and epidermal growth factor-induced DNA synthesis. The stimulatory effect of serotonin on the growth factor-induced DNA synthesis was inhibited by ketanserin. The amount of serotonin contained in WBS was sufficient to induce the phospholipase C reaction and stimulate the growth factor-induced DNA synthesis. These results indicate that serotonin plays a major role in the WBS-induced phospholipase C-mediated hydrolysis of phosphoinositides and DNA synthesis in rabbit VSMCs and suggest that serotonin may act as an important growth regulator for VSMCs in addition to acting as a vasoconstrictor.
Atherosclerosis 1990 Jul
PMID:Serotonin plays a major role in serum-induced phospholipase C-mediated hydrolysis of phosphoinositides and DNA synthesis in vascular smooth muscle cells. 216 88

We tested the hypothesis that atherosclerosis potentiates coronary vasoconstriction to serotonin and ergonovine. Coronary microvascular pressures and diameters were measured in the beating left ventricle in normal and atherosclerotic cynomolgus monkeys. Pressures were measured in arteries (190-350 microns diam) that were distal to atherosclerotic lesions. Microvascular pressure and simultaneous measurements of aortic pressure and myocardial blood flow were used to calculate segmental vascular resistance (large artery resistance and microvascular resistance) during serotonin, phenylephrine, and ergonovine dosages. Aortic pressure was maintained constant during all interventions. Administration of phenylephrine (50 micrograms.kg-1.min-1 iv) produced a similar increase in microvascular resistance from base line (P less than 0.05) in atherosclerotic and normal animals, 26 +/- 5 and 14 +/- 9 mmHg.min.g.ml-1, respectively. Serotonin (50 micrograms/min) did not influence coronary resistance in normal animals but produced a significant increase in both large artery (8 +/- 3 mmHg.min.g.ml-1) and microvascular resistance (21 +/- 6 mmHg.min.g.ml-1) in atherosclerotic animals (P less than 0.05). A higher dose of serotonin (200 micrograms/min) produced a modest increase in large artery resistance from base line in normal animals (3 +/- 1 mmHg.min.g.ml-1) and a greater increase in atherosclerotic animals (9 +/- 4 mmHg.min.g.ml-1) (P less than 0.05 vs. normals). Ergonovine (10 micrograms.kg-1.min-1 iv) elevated microvascular resistance in both normal and atherosclerotic animals (P less than 0.05) but increased large artery resistance only in atherosclerotic animals (10 +/- 4 mmHg.min.g.ml-1) (P less than 0.05). In summary, coronary vasoconstrictor responses to serotonin and ergonovine were potentiated by atherosclerosis. Because augmented constrictor responses to serotonin were observed in both the diseased arteries and the microcirculation of atherosclerotic animals, we speculate that the pathophysiological consequences of atherosclerosis extend into the microcirculation.
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PMID:Effects of atherosclerosis on the coronary microcirculation. 230 17

To determine whether platelets contribute to the development of atherosclerosis, we compared the severity of atherosclerosis in susceptible C57BL/6 mice carrying either a normal or a variant phenotype for platelet function. Five genetically distinct mutants with increased bleeding times and abnormal dense granules were used: maroon (ru-2mr), light ear (le), ruby eye (ru), beige (bg1), and pale ear (ep). After a 14-week consumption of an atherogenic diet, three mutants had significantly less disease involvement than the control: light ear, maroon, and ruby eye. In contrast, pale ear ahd lesions similar to control animals. After 48 weeks, the two mutants with the least degree of atherosclerosis at 14 weeks, light ear and ruby eye, showed greater than 50% survival. In contrast, no animals from the beige, pale ear, or the normal C57BL/6 strains survived. To determine whether a specific biochemical component of platelet function is related to atherosclerosis, we measured serotonin found in dense granules. Serotonin showed no correlation with each mutant's atherosclerosis susceptibility. These results indicate that some particular component of platelet function affects atherosclerosis. That component is intact in pale ear, moderately affected in beige and maroon, and severely affected in light ear and ruby eye. The identity of that component remains an interesting question whose answer may provide further insight into the atherosclerotic disease process.
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PMID:Analysis of atherosclerosis susceptibility in mice with genetic defects in platelet function. 236 71

When the local concentration of serotonin is raised during platelet aggregation, the direct effect of serotonin on vascular smooth muscle is to activate the contractile process. Serotonin also amplifies the constrictor responses to other neurohumoral mediators. Vascular smooth muscle can become hyperreactive to the vasoconstrictor effects of serotonin both acutely (e.g., local cold, hypoxia) and chronically (e.g., atherosclerosis, hypertension). Vasodilator responses to serotonin can be unmasked by blockade of its vasoconstrictor component. The inhibition by ketanserin of the various vasoconstrictor and platelet-aggregating effects of serotonin presumably contributes to the therapeutic effects of the compound.
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PMID:Serotonin and the blood vessel wall. 241 58

The present article deals with the pathophysiological role of serotonin in cardiovascular disease and in other disorders that are accompanied by cardiovascular pathophysiological events. The distribution of serotonin over various organs and tissues and the presence of several types of 5-HT receptors would suggest a rather important physiological role of serotonin. However, a modest serotonergic role could only be shown for the microcirculation and for the regional circulation of the brain and the intestinal wall. An important pathological role of serotonin in the carcinoid syndrome, in migraine, and in peripheral vascular disease is beyond debate, although many details remain to be established. The possibility that serotonergic mechanisms contribute to Raynaud's phenomenon and other vasospastic disorders is the subject of present discussions, although firm evidence for this view is not widely available. An involvement of peripheral serotonin in the genesis and maintenance of essential hypertension seems very unlikely, although vascular damage due to hypertension is probably enhanced by serotonin released from aggregating platelets. This ancillary process is, in particular, to be anticipated in older patients, with vascular walls predamaged by atherosclerosis. For this reason, pharmacological blockade of 5-HT2 receptors may be of potential therapeutic benefit in this category of patient. Finally, the involvement of central serotonergic mechanisms in hypertensive disease cannot be ruled out.
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PMID:Pathophysiological relevance of serotonin. 244 63

Serotonin metabolism was investigated in 15 patients (8 women, 7 men) with decreased renal function (clearance of endogenous creatinine = 0.07-0.74 ml/s) and compared to the values obtained in healthy controls. In spite of thrombocytopenia, the patients' platelet serotonin concentrations (1.99-47.6 nmol/10(9) platelets) as well as the plasma serotonin levels (190-2,176 nmol/l) were significantly higher than in controls (1.36-7.87 nmol/10(9) platelets, p less than 0.05; 0-500 nmol/l, p less than 0.001). The low urinary serotonin output (0-414 to 167-1,187 nmol/24 h in controls, p less than 0.001) probably reflects its decreased synthesis in the residual renal parenchyma. 5-Hydroxyindolacetic acid was excreted in normal amounts. The impairment in serotonin metabolism is closely correlated with the decrease in renal function. The data document accumulation of serotonin in the circulation. This impairment could contribute to platelet hyperaggregation and/or consumptive hypocoagulation, maintenance of hypertension, and acceleration of atherosclerosis.
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PMID:Serotonin metabolism in patients with decreased renal function. 247 19

Vasoconstrictor responses are augmented in porcine coronary arteries in hypercholesterolemia and atherosclerosis, leading to an occurrence of coronary vasospasm in the latter condition. The role of the endothelium in the vascular hyperreactivity in hypercholesterolemic and atherosclerotic coronary arteries was examined, particularly in response to aggregating and related vasoactive substances. Male Yorkshire pigs underwent balloon endothelial denudation of the left anterior descending coronary artery (LAD) and 2% high-cholesterol feeding for 10 weeks. Electron microscopic examination demonstrated a full lining of endothelial cells in the LAD and the left circumflex coronary artery (LCX). Endothelium-dependent responses were examined in vitro. In cholesterol-fed animals, endothelium-dependent relaxations to aggregating platelets, serotonin, ADP, bradykinin, thrombin, and the calcium ionophore A23187 were depressed in LAD (atherosclerosis), while the relaxations to aggregating platelets, serotonin and ADP were depressed in LCX (hypercholesterolemia). Serotonin-induced contractions were endothelium-dependently augmented in atherosclerotic LAD; the endothelium-dependent component of the contractions was inhibited by blockers of cyclooxygenase. Bioassay studies demonstrated a depressed release of endothelium-derived relaxing factor(s) from the atherosclerotic LAD in response to serotonin. These experiments indicate that the endothelium-dependent relaxations to aggregating platelets and related vasoactive substances are severely impaired in atherosclerosis and moderately impaired in hypercholesterolemia. Since coronary atherosclerosis was induced by a combination of balloon endothelial injury (and regeneration) and high-cholesterol feeding in this study, the combined effects of those factors must account for the severely impaired responses in atherosclerosis. The depressed release of the endothelium-derived relaxing factor(s) and the concomitant release of vasoconstrictor product(s) of cyclooxygenase appear to be responsible for the impaired relaxations.
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PMID:Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosis. 249 69

In a multi-center, double-blind, placebo-controlled trial in claudicating patients with peripheral atherosclerosis, the effects of 1 year of treatment with ketanserin (20 mg t.i.d. for 1 month, 40 mg t.i.d. thereafter; n = 63 patients) or placebo (n = 84 patients) on platelet function (aggregation in P.R.P. by 5-HT 5 x 10(-6) M, ADP 1 to 5 x 10(-6) M, collagen 2 micrograms/ml; platelet 5-HT content; plasma beta TG- and PF4-levels; serum TXB2) were analyzed. Before treatment, claudicating patients (n = 173) displayed an higher reactivity of platelets to 5-HT and signs of platelet activation/release in vivo (higher plasma beta TG-PF4, lower platelet 5-HT content and decreased platelet aggregation by ADP, collagen) in comparison with healthy controls (n = 50). After 1 year of treatment with ketanserin, but not with placebo, platelet aggregation induced by 5-HT (slope -41.1%) and platelet 5-HT content (-23.7%) were significantly reduced. PF4 and beta TG were significantly higher than their pre-medication values in the two trial groups. The other platelet function tests were not significantly modified by the treatment. Only the small subgroup of patients with initially elevated plasma beta TG levels (greater than 20 ng/ml) also scrutinized for hidden NSAID consumption or technical bias (exclusion of data with serum TXB2 less than or equal to 10000 pg/100 microliters and/or plasma PF4 greater than 10 ng/ml) had significantly lower plasma beta TG levels (-22.7%) than the pre-medication values after treatment with ketanserin, but not with placebo. The present study confirms that ketanserin affects some platelet functions, during long-term administration in claudicating patients with atherosclerosis.
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PMID:Platelet function during long-term treatment with ketanserin of claudicating patients with peripheral atherosclerosis. A multi-center, double-blind, placebo-controlled trial. The PACK Trial Group. 252 41


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