Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible role of 5-hydroxytryptamine (5HT) and 5HT-receptors in hypertension, already suggested by Page in 1954, has been subject to a renaissance of interest owing to the development of antihypertensive drugs which interact with 5HT-receptors. These drugs, like ketanserin, urapidil and flesinoxan are used as tools to study the role of 5HT and its receptors in hypertension. Some arguments would plead in favour of a certain role of 5HT and 5HT-receptors in the pathogenesis and maintenance of hypertension: hyperresponsiveness of blood vessels from hypertensive patients and animals to 5HT-induced constriction; the antihypertensive/vasodilator activity of the 5HT2-receptor antagonist ketanserin; enhanced sensitivity of platelets from hypertensives to 5HT. However, there are also several arguments which do not support a causal role of 5HT in hypertensive disease: 5HT is not a generally accepted pressor agent, whereas its concentration in the circulating blood is subthreshold; the 5HT2-receptor antagonist ketanserin is the only agent of this type which lowers blood pressure, other 5HT2-receptor blockers (ritanserin; LY 53587) being inactive. The various data and arguments available do not unequivocally support a relevant role of peripheral 5HT and its receptors in hypertensive disease. 5HT2-receptor blockade may, however, have a favourable effect on the microcirculation under pathological conditions. The stimulation of central 5HT1A-receptors by drugs like urapidil, 8-OH-DPAT or flesinoxan, has been demonstrated to induce peripheral sympathoinhibition and a fall in blood pressure. This mechanism appears to be a novel target for centrally acting antihypertensives, clearly different from that of clonidine and related drugs, which are centrally acting alpha 2-adrenoceptor agonists.
 ...
PMID:Serotonergic receptors and drugs in hypertension. 135 65

To investigate possible alterations in 5-hydroxytryptamine (5HT) kinetics and sensitivity of blood platelets in patients with essential hypertension, 45 essential hypertensive patients and 45 normotensive healthy subjects matched in pairs for age, sex, and smoking status were compared. There were 18 women and 27 men in each group, ranging from 30 to 73 years of age. Results of essential hypertensive patients differed in several ways from those of normotensive subjects. In essential hypertensive patients, maximal 5HT uptake velocity (Vmax) decreased with increasing blood pressure and age and was reduced the most in older men. Vmax was positively related to the EC50 of 5HT for inducing a shape change reaction. In essential hypertensive patients, both Vmax of 5HT uptake and the EC50 of 5HT for shape change showed positive correlations with the 5HT content in platelets; the former relation was different between the essential hypertensive and normotensive groups (F = 5.53; p = 0.02). These results indicate reduced uptake of 5HT by blood platelets and suggest enhanced 5HT plasma concentrations in local areas, especially vascular lesions in essential hypertensive patients. Increased periplatelet concentrations of 5HT may lead to preactivation of platelets and possibly stimulation of vascular smooth muscle via their 5HT2-receptors. These changes are likely to be involved in the pathogenesis of increased thromboembolic complications in essential hypertensive patients, particularly in older men.
Hypertension 1990 Mar
PMID:5-Hydroxytryptamine kinetics and activation of blood platelets in patients with essential hypertension. 213 32

Serotonin (5HT) released from activated platelets causes platelet aggregation and vasoconstriction which are both exaggerated in older age and contribute to the development of thromboembolic complications. Platelet 5HT kinetics and reactivity were investigated in 45 patients with essential hypertension and 45 healthy control subjects matched for age, sex and smoking status. An age-dependent attenuation of total 5HT turnover and platelet 5HT release was revealed in control subjects but not in patients with essential hypertension. In the latter, especially in men, platelet 5HT uptake decreased with age and high blood pressure, leading to elevated 5HT plasma concentration. In parallel, platelet reactivity was increased with advancing age as shown by a greater 5HT induced aggregation and higher beta-thromboglobulin plasma concentration. Antihypertensive treatment with ketanserin resulted in inhibition of 5HT-induced shape change reaction and aggregation as well as a decrease in platelet 5HT release. Age contributes to altered platelet 5HT kinetics and 5HT2-receptor reactivity thereby elevating thromboembolic risk. 5HT2-receptor blockade with ketanserin interferes with these events by inhibition of platelet 5HT release and by a greater antiaggregatory and antihypertensive action in older age.
 ...
PMID:Age, platelet serotonin kinetics and 5HT2-receptor blockade in essential hypertension. 225 91

The cause of preeclampsia, a syndrome unique to human pregnancy, is unknown. There is presently no effective pharmacologic therapy once the symptoms have appeared. Only delivery is curative. Preeclampsia likely has multiple etiologies, each of which activates a common pathway, culminating in diffuse endothelial damage, vasospasm, and hypertension. Current investigation suggests that serotonin has a pivotal role in the genesis of preeclamptic hypertension. The evidence, as obtained from human and animal study, is reviewed in this article, and areas in need of further study are highlighted. A modified series of Koch's postulates is employed for a framework. Serotonin is the agent but does not directly cause the hypertension. Rather, it is suggested that in a milieu characterized by a reduction in endothelial-derived relaxing factor and prostacyclin, serotonin augments the smooth muscle response to normally occurring concentrations of endogenous vasopressors. It is delivered to the site of action (the microvasculature) by the platelet, whose aggregation is encouraged by dysfunctional endothelium. Either inhibition of the delivery mechanism by a low, daily dose of aspirin, or inhibition of the peripheral serotonin type 2 (5HT2) receptor, effectively controls the hypertension.
 ...
PMID:The role of serotonin in the preeclampsia-eclampsia syndrome. 228 49

The role of serotonin in the pathogenesis of hypertension is interesting, and its investigation is much in vogue at present. This study compared the hypotensive effect of ketanserin, a specific 5-hydroxytryptamine receptor antagonist, with metoprolol in essential hypertension. On a double-blind basis, one treatment group (19 patients on ketanserin) was compared with another (21 patients on metoprolol). There was a significant reduction in diastolic blood pressure with both ketanserin and metoprolol (P less than 0,001). Side-effects were insignificant. One patient on metoprolol and 2 on ketanserin complained of dizziness. The dose of ketanserin was 40 mg twice a day and that of metoprolol 100 mg twice a day. Ketanserin does not appear to cause abnormal haematological values or biochemical adverse effects. It can be given to hypertensive patients with cardiac failure or bronchial asthma without adverse effects and may improve the peripheral vascular status of a hypertensive patient.
 ...
PMID:A comparative study of ketanserin and metoprolol in essential hypertension. 293 40

The role of serotonin (5HT) in the pathogenesis of ACTH-induced hypertension in sheep has been examined. The pressor responses to injections of 5HT (0.1-30 micrograms/kg) were similar in normotensive and hypertensive sheep. Prior treatment with the 5HT2 receptor antagonist ketanserin had no effect on the development of hypertension produced by ACTH administration.
 ...
PMID:Ketanserin does not prevent ACTH-induced hypertension in sheep. 298 38

Ketanserin is an agent whose main pharmacologic action is antagonism of serotonin (5-hydroxytryptamine, 5HT) receptors of the 5HT2 subtype. It also has weak alpha 1-adrenergic blocking properties, which may contribute to the acute blood pressure lowering effects seen in animal models of hypertension. During chronic treatment of hypertension in animals, the 5HT2 antagonistic properties, or a combination of 5HT2 and alpha 1-antagonistic effects, seems to be responsible for ketanserin's hypotensive action. Studies of patients with hypertension have demonstrated the therapeutic effects of ketanserin in monotherapy and combination therapy. In humans, the drug has a terminal half-life of 12-25 hours, and a twice daily dosage will lower blood pressure over the day. Ketanserin is a vasodilator that acts on both resistance and capacitance vessels. Chronic treatment with the drug causes minimal reflex changes in cardiovascular function, as well as sustained blood pressure reduction comparable with the effects of beta-adrenergic blockers or diuretics. In elderly patients, the therapeutic effects of ketanserin appear to be greater, and side effects are less frequent compared with beta-blockers and diuretics. In addition to its antihypertensive action, ketanserin also produces other effects that may be important in reducing cardiovascular morbidity and mortality in patients with hypertension. Some studies have shown a reduction in total and low-density lipoprotein (LDL) cholesterol, and a rise in high-density lipoprotein (HDL) cholesterol. Ketanserin also reduces ex vivo platelet aggregation and inhibits the serotonin-induced platelet release reaction. Worldwide experience with ketanserin in the treatment of hypertension indicates that it is a safe and effective agent for long-term therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of a new serotonin antagonist, ketanserin, in experimental and clinical hypertension. 304 35

The 5-hydroxytryptamine (5HT)-system of human blood platelets consists of a relatively specific uptake mechanism for 5HT at the plasma membrane, intracellular storage organelles (dense bodies), a metabolizing enzyme (monoaminoxidase B) and a 5HT2-receptor whose stimulation leads to activation of the phosphatidylinositide turnover, a rise in free cytoplasmic Ca2+, phosphorylation of proteins and a shape change reaction. There is neither a relevant 5HT-biosynthesis nor a marked physiological 5HT-turnover in platelets. Under physiological conditions the platelet 5HT-system may have a role as a scavenger for free extracellular 5HT and in hemostasis. Disturbances which have been described in pathophysiological states include impairment of 5HT-uptake (hypertension, migraine), impairment of 5HT-storage (storage pool deficiencies, thromboembolic disorders, hypertension) and increased sensitivity to activating agents like 5HT (cardiovascular disorders, diabetes). Besides their role in physiology and pathophysiology platelets may be useful partial models for vascular smooth muscle cells.
 ...
PMID:The 5-hydroxytryptamine system of blood platelets: physiology and pathophysiology. 381 34

In vitro affinity for vascular 5HT2 and alpha receptors was determined for several compounds (spiperone, ketanserin, mianserin, trazodone, mepiprazole, benzoctamine, m-trifluoro-methylphenylpiperazine, m-chlorophenylpiperazine, and 1-(1-naphthyl)piperazine) known to interact with serotonin receptors. All compounds competitively inhibited 5HT2 and alpha receptors with differing degrees of selectively. Based on these observations, ketanserin, benzoctamine, and 1(1-naphthyl)piperazine were evaluated as antihypertensive agents in spontaneously hypertensive rats (SHR). Of these compounds, 1-(1-naphthyl)piperazine was a highly selective 5HT2 receptor antagonist with a ratio of 5HT2 to alpha receptor affinity of greater than 2000. The ratio of 5HT2 to alpha receptor affinity for ketanserin and benzoctamine was 63 and 16, respectively. However, the order of affinity toward 5HT2 receptors was ketanserin greater than 1-(1-naphthyl)piperazine greater than benzoctamine whereas the order of affinity toward alpha receptors was ketanserin greater than benzoctamine greater than 1-(1-naphthyl)piperazine. A similar order of potency toward both 5HT2 and alpha receptors was found in pithed SHR based on antagonism of the pressor response to serotonin and methoxamine, respectively. In the SHR, maximum blood pressure reduction at a dose of 10 mg/kg i.p. was approximately 65 and 30 mm Hg for ketanserin and benzoctamine, respectively; 1-(1-naphthyl)piperazine did not affect blood pressure. Thus, blood pressure reduction more closely paralleled the in vitro and in vivo potency of these agents toward vascular alpha rather than 5HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Evidence that blood pressure reduction by serotonin antagonists is related to alpha receptor blockade in spontaneously hypertensive rats. 631 38

Ketanserin, a 5HT2-receptor blocking drug was given to 17 patients with essential hypertension. Satisfactory control was achieved in 13 patients. Control was not as satisfactory when given once daily. There was no rebound effect when the drug was ceased. Side-effects were few. Ketanserin was a satisfactory drug to reduce blood pressure in patients with moderate hypertension.
 ...
PMID:The effect of ketanserin in essential hypertension. 662 48


1 2 3 4 5 Next >>