Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0085580 (
essential hypertension
)
14,686
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To investigate if there can be alterations in the
5-hydroxytryptamine
(
5-HT
) uptake system in the sensitivity of platelets in patients with
essential hypertension
, 38 hypertensive patients and 37 normotensive healthy subjects were compared. In patients, the maximal
5-HT
uptake velocity was reduced. The density of binding sites for 3H-imipramine was elevated in hypertensive females, but unchanged in males. The sensitivity of
5-HT
uptake to trazodone was unchanged in patients. Half-maximal concentrations of
5-HT
for inducing a shape change reaction of platelets were positively correlated with diastolic blood pressure in male patients and were reduced in female mild hypertensives. It is suggested that these changes are likely to be involved in the pathogenesis of hypertension.
...
PMID:[Function of the serotoninergic system of blood platelets in patients with hypertension]. 129 66
1. To examine the pathophysiological significance of
5-hydroxytryptamine
(serotonin) in
essential hypertension
, we compared the renal response to intrarenally formed
5-hydroxytryptamine
by oral dosing with its precursor, L-tryptophan (2 g), in nine patients with
essential hypertension
and in six subjects with normotension. 2. Before tryptophan administration, urinary excretion of
5-hydroxytryptamine
was significantly higher in the hypertensive group than in the normotensive group (66 +/- 8 versus 36 +/- 6 ng/min, P less than 0.05), whereas renal plasma flow and glomerular filtration rate did not differ between the two groups. After dosing with tryptophan, urinary excretion of
5-hydroxytryptamine
significantly increased to the same plateau level in both groups (366 +/- 55 ng/min in the hypertensive group and 365 +/- 64 ng/min in the normotensive group). Significant and equivalent decreases in renal plasma flow were observed in the early phase after tryptophan administration in both groups (-8.5 +/- 3.4% in the hypertensive group and -8.2 +/- 1.7% in the normotensive group). Thereafter, renal plasma flow increased to above the baseline value in normotensive subjects, whereas this late vasodilatation was absent in the hypertensive group. Glomerular filtration rate significantly decreased at the time of the fall in renal plasma flow in the normotensive group (106.8 +/- 7.8 to 92.7 +/- 8.5 ml min-1 1.73 m-2, P less than 0.05), whereas it remained unchanged in the hypertensive group (108.2 +/- 6.2 to 110.4 +/- 6.3 ml min-1 1.73 m-2, not significant).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Altered renal response to enhanced endogenous 5-hydroxytryptamine after tryptophan administration in essential hypertension. 131 65
Serotonin (
5-hydroxytryptamine
; 5HT) kinetics and platelet activation by 5HT were studied in patients with
essential hypertension
(n = 45), and in matched normotensive subjects (n = 45). Platelet response to 5HT and plasma beta-thromboglobulin increased with age in men, both normotensives and hypertensives. Beta-thromboglobulin and 5-hydroxyindoleacetic acid (5HIAA) excretion were higher in hypertensive men than in women. In women, no changes in platelet activity or 5HIAA excretion were found. 5HT plasma concentrations increased with blood pressure. Platelet 5HT uptake (Vmax and KM) were the lowest in hypertensive men greater than or equal to 60 years of age. This may indicate that 5HT uptake in vivo in normotensives is far below maximum (VNT much less than Vmax), whereas in hypertensive men it may be close to maximum (VHT approximately Vmax). This could reflect significantly higher 5HT plasma concentrations in vivo hypertensives than in normotensives. The reduced uptake (which was found only in hypertensive men) may indicate an insufficient compensation of the enhanced 5HT release from aggregating platelets in older men, in whom platelet activity is enhanced in vivo. It is concluded that the defect in platelet 5HT uptake in hypertensives--along with the enhanced platelet aggregation--may contribute to a critical increase in 5HT plasma concentrations locally. An increase in 5HT concentrations leads to biochemical changes (higher 5HIAA excretion) as well as to an enhanced stimulation by 5HT. This may be of clinical relevance especially in older men, in whom 5HT2-receptor mediated responses are enhanced.
...
PMID:Impaired uptake of 5 hydroxytryptamine platelet in essential hypertension: clinical relevance. 170 94
Seventeen normotensive, premenopausal women were treated with the
5-hydroxytryptamine
-reuptake inhibitor dexfenfluramine 30 mg per day, for 4 days in a randomised double-blind, cross-over, placebo controlled trial. Energy intake was held constant during the study as the aim was to study the endocrine and metabolic effects of dexfenfluramine dissociated from its weight-lowering properties. Body weight, blood glucose, plasma insulin, cholesterol triglycerides and C-peptide after an overnight fast and during an oral load of 100 g glucose did not change after dexfenfluramine compared to placebo. Supine and standing systolic and diastolic blood pressures were significantly decreased, while heart rate remained unchanged. Plasma noradrenaline and plasma renin were markedly reduced by dexfenfluramine, and cortisol, beta-endorphin and thyroid hormones were not changed. Thus, dexfenfluramine has a significant hypotensive effect in normotensive, obese women after 4 days of treatment, independent of a negative energy balance. This was associated with decreased circulating plasma noradrenaline, indicating decreased sympathetic nerve activity. Dexfenfluramine may be a candidate drug for longer-term trials in the treatment of
primary hypertension
associated with obesity.
...
PMID:Haemodynamic, metabolic and endocrine effects of short-term dexfenfluramine treatment in young, obese women. 206 May 60
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.
...
PMID:Pathophysiological and pharmacotherapeutic aspects of serotonin and serotonergic drugs. 213 70
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.
...
PMID:5-Hydroxytryptamine kinetics and activation of blood platelets in patients with essential hypertension. 213 32
The antihypertensive effect of ketanserin, a recent
5-hydroxytryptamine
(
5-HT
) antagonist, which acts on the 5-HT2-subtype receptor, was evaluated in 10 patients of both sexes (age range 35-69 years) with mild to moderate
essential hypertension
. Blood pressure and heart rate were measured at rest, in supine and standing position at the end of two weeks of placebo washout and after 2, 4 and 8 weeks of treatment with ketanserin 20 mg twice daily as monotherapy, while the changes of blood pressure and heart rate during static (hand-grip) and dynamic (bicycle ergometer) exercise were evaluated at the end of placebo and of the fourth week of therapy. The treatment induced a highly significant reduction of supine and standing systolic and diastolic blood pressure during rest, without any significant change in heart rate. During dynamic exercise, the increase in systolic and diastolic blood pressure and heart rate was not blunted by ketanserin, while the drug reduced systolic blood pressure and heart rate increase, during static exercise, with no change of diastolic blood pressure. From these data it may be concluded that ketanserin lowers blood pressure in
essential hypertension
without any interference with cardiovascular reflexes related to standing or dynamic exercise, and reduces the increase of systolic blood pressure and heart rate during static exercise with favourable interference on myocardial oxygen consumption. This sparing effect on myocardial oxygen demand is particularly relevant in hypertensive patients with asymptomatic coronary disease engaged in normal daily physical activity which includes many forms of static exercise.
...
PMID:[Effects of ketanserin on arterial pressure at rest and during physical exercise in essential arterial hypertension]. 252 82
Ketanserin, an antagonist highly selective for
5-hydroxytryptamine
(serotonin) type 2 (S2) receptors, was given as monotherapy in a dose of 40 mg b.i.d. to 24 subjects with mild to moderate
essential hypertension
. Its effects were evaluated in a placebo-controlled double-blind crossover study. The effect on blood pressure in 18 subjects was monitored by 24-hour ambulatory intra-arterial measurements. Systolic and diastolic intra-arterial pressures were significantly lowered by ketanserin both during the day and at night, whereas heart rate was unchanged. Cuff pressure readings (triplicate measurements) with the London School of Hygiene sphygmomanometer and an automatic device (12 measurements in 1 hour) in the outpatient clinic also showed a significant effect on both supine and standing pressures. No postural hypotension was noted. Ketanserin had no effect on endogenous creatinine clearance, serum cholesterol levels, and the plasma levels of norepinephrine, renin, and aldosterone. The only side effect that was significantly more common with ketanserin than with placebo treatment was an increase in body weight. Ketanserin may have a place in the treatment of mild to moderate
essential hypertension
.
...
PMID:Chronic effect of ketanserin in mild to moderate essential hypertension. 293 97
Abnormal pressor responses are known to occur in the maternal circulation in pregnancy-induced hypertension (PIH), but little is know of the response of the foetal circulation. The responsiveness of umbilical arteries in PIH can be studied after delivery, and this is a useful model to explore the pathophysiological mechanisms involved. In the present experiments, the in vitro response of umbilical artery rings to bradykinin and
5-hydroxytryptamine
(
5-HT
) was tested and ultrastructural changes investigated. Umbilical arteries from 48 cords were studied. Fifteen of the mothers had PIH, five had
essential hypertension
pre-dating the pregnancy and five had diabetes. Twenty-three women had pregnancies uncomplicated by hypertension or serious medical or obstetric problems and these served as controls. Umbilical arteries from the severe proteinuric PIH group were significantly more responsive to
5-HT
as assessed by affinity constants (P less than 0.05). The responsiveness of arteries from all other groups did not differ from the normal cases. A probable mechanism for the findings is endothelial damage as a result of pre-eclamptic disease. This was substantiated by ultrastructural evidence.
...
PMID:Umbilical artery reactivity and ultrastructural changes in pregnancy-induced hypertension and other complicated pregnancies. 342 82
The present study examines the putative role of serotonin (
5-hydroxytryptamine
) in the pathogenesis of
essential hypertension
. Intraplatelet and plasma free serotonin levels, as well as the amounts released from aggregating platelets, were measured in six patients with untreated
essential hypertension
, using high performance liquid chromatography with electrochemical detection. Platelet serotonin contents were similar to those in age-matched controls. However, hypertensive patients showed significantly higher levels of plasma free serotonin as well as a significantly higher release from aggregating platelets, stimulated by collagen or adenosine diphosphate (ADP). These data suggest that serotonin may be involved in the pathogenesis of
essential hypertension
.
...
PMID:Serotonin levels in hypertension. 345 3
1
2
Next >>