Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Serotonin (5HT) constricts large arteries in vitro, an effect which seems contrary to 5HT-induced increases in blood flow observed in vivo. We used angiography to assess large artery responses, and blood flow (Q, electromagnetic flowmeter) to assess arteriolar responses to 5HT, norepinephrine (NE), and antagonists in the femoral circulation of the intact, anesthetized dog. 5HT constricted large arteries at a threshold dose of less than 10 micrograms/min, giving a 45 +/- 3% reduction of popliteal artery diameter at 100 micrograms/min (p less than 0.001). NE failed to constrict large arteries. With 100 micrograms/min 5HT, Q increased (delta Q = 108 +/- 26 ml/min; p = 0.001). NE decreased Q. Ketanserin, a 5HT and alpha 1-adrenergic antagonist, exerted a dose-dependent inhibition of 5HT-induced large artery constriction. Methysergide partially blocked the 5HT-induced large artery constriction. Ketanserin potentiated the Q response to 5HT whereas higher doses of methysergide reduced the Q response to 5HT. Neither indomethacin nor propranolol altered either response. Failure of NE to constrict large arteries in vivo and ketanserin antagonism of constriction produced by 5HT suggest the response to 5HT involves the 5HT2 receptor. No role for the 5HT2 receptor in blood flow responses is suggested. These observations may have implications for therapy of occlusive vascular disease.
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PMID:Differential large and small vessel responses to serotonin in the dog hindlimb in vivo: role of the 5HT2 receptor. 258 Jan 49

Platelet activation and aggregation appear to play an important part in the development of vascular disease. We studied the effect of varying sodium intake on total plasma serotonin and in vitro aggregation of blood platelets. A total of 12 normal female volunteers were studied after 5 days on a 10 or 200 mmol/day sodium diet. Aggregation studies were performed by incubating stirred platelet-rich plasma (PRP) with adenosine diphosphate (ADP) at final concentrations of 1 and 4 mumol/l; we also studied the effect of pre-incubating PRP with ketanserin or saralasin (1 mumol/l and 1 nmol/l final concentration, respectively). Salt-loading produced a significant increase in platelet aggregation induced by both 1 and 4 mumol/l ADP, and also a significant fall in PRP in serotonin concentration; since there was also a significant drop in the yield of platelets in PRP during salt-loading, the difference in serotonin concentration was not significant when expressed as pmol serotonin/10(8) platelets. There was a significant negative correlation between log serotonin levels (nmol/l) and % aggregation induced by 4 mumol/l ADP. Ketanserin decreased aggregation (induced by 4 mumol/l ADP) in PRP obtained during high salt intake; saralasin had no effect on aggregation, but did cause a decrease in light transmission. These results indicate that in normal females: (1) in vitro platelet aggregation is increased with high sodium intake, and this effect was reduced by addition of ketanserin; (2) PRP platelet count and total plasma serotonin levels are both significantly altered by changes in sodium status; (3) aggregation (%) is inversely proportional to log serotonin concentration (nmol/l).
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PMID:High sodium intake increases platelet aggregation in normal females. 348 16

Ketanserin was used in a randomized double-blind trial in 15 patients with Raynaud's phenomenon in progressive systemic sclerosis (PSS). Its effect on Raynaud's phenomenon was evaluated by IR-radiometry, Doppler ultrasound, nailfold capillaroscopy, frequency of finger ulcerations and patient complaints before and after a 3-month course of treatment with oral ketanserin in the dosage of 60 mg daily in the first month and 120 mg in the second and third months. Of the 8 patients treated with ketanserin, 5 showed improvement. In the other 2 patients with progression of skin sclerosis and multiorgan involvement, the peripheral vascular disorder was unchanged. Ketanserin treatment was discontinued in one patient owing to dizziness and anxiety. In one patient ketanserin was reduced to 60 mg daily because of fluid retention. There were no other adverse effects. In 7 control patients on placebo there was no significant improvement in Raynaud's phenomenon. Ketanserin, a selective, specific and pure antagonist of 5-hydroxytryptamine (serotonin) appears to be an effective agent in the treatment of Raynaud's phenomenon and digital ischaemic ulcers in PSS. Moreover, ketanserin could contribute to the understanding of the role of 5-hydroxytryptamine in PSS pathogenesis.
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PMID:Effect of ketanserin on Raynaud's phenomenon in progressive systemic sclerosis: a double-blind trial. 391 37