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

The aim of this study was to investigate if the endothelium-dependent relaxation and the inhibitory effect of endothelium against vasoconstrictor stimuli are reduced by aging and hypertension in rat aorta. Both relaxation and isometric contraction of intact and denuded aortic rings from spontaneously hypertensive rats (SHR) of 7-9, 12-18, 28-36 and more than 70 weeks old and from age-matched Wistar-Kyoto rats (WKY) were measured in parallel. An age-related decrease of endothelium-dependent relaxation to acetylcholine was found, which was greater in arteries from SHR (p < 0.05). Indomethacin normalized the endothelium-dependent relaxations in aortic rings from either old or hypertensive rats. Relaxations elicited by nitroglycerin were slightly enhanced with age in both WKY and SHR (p < 0.05). Moreover, endothelium removal increased responsiveness to indanidine and to 5-hydroxytryptamine (5-HT). Endothelium-dependent inhibition on the contraction decreased with aging (to a greater extent in SHR). These results indicate that aging and hypertension are associated with a decrease in the endothelium-dependent responses. Endothelium-dependent relaxations of aortae from old normotensive and hypertensive rats were impaired by the production of a cyclooxygenase-derived contractile factor. However, the higher response to nitroglycerin suggests a lesser production of endogenous nitric oxide by endothelial cells.
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PMID:Changes in endothelium-dependent vascular responses associated with spontaneous hypertension and age in rats. 884 47

Cells rely on gap junctions for intercellular communication, which is important for growth and contractility. For example, gap junctional communication in the uterus increases near parturition, with a concomitant increase in oscillatory contractions. Because arterial responsiveness to contractile agonists is increased in hypertension, we tested the hypothesis that gap junctional communication is increased in hypertension. We examined thoracic aortas from deoxycorticosterone acetate (DOCA)-salt hypertensive and sham normotensive rats using isolated tissue baths and Western blotting techniques. The concentration of 5-hydroxytryptamine necessary to produce a threshold response was significantly lower in aortas from DOCA-salt (4 nmol/L) compared with sham (100 nmol/L) rats; this was also true for norepinephrine and KCl. In these same aortas, the appearance of spontaneous oscillatory contractions, which are sensitive to the gap junctional inhibitor heptanol (0.3 mmol/L), was more frequent in DOCA-salt arteries (93% versus 14% in sham). Heptanol (1 mmol/L) normalized the DOCA-salt aortic contraction to 5-hydroxytryptamine to levels similar to those of the response of the sham aorta in the presence of heptanol. Western analyses revealed that the density of connexin43 immunoreactivity, the connexin being a constituent of gap junctions, was found to be threefold more abundant in aortic homogenates of DOCA-salt rats compared with that of sham rats. This finding supports the hypothesis that gap junctional communication is increased in hypertension, at least at the protein level. We speculate that this increase results in a portion of the increased vascular reactivity and appearance of contractile oscillations in vascular smooth muscle.
Hypertension 1996 Nov
PMID:Vascular gap junctional communication is increased in mineralocorticoid-salt hypertension. 926 Sep 98

To explore the importance of brain serotonin (5-hydroxytryptamine) in the heatstroke-induced cerebral ischemia and neuronal injury, we evaluated the effects of heatstroke on brain serotonin release, survival time, cerebral hemodynamic changes, and neuronal cell damage in rats with or without brain serotonin depletion produced by 5,7-dihydroxytryptamine. In vivo voltammetry was used to measure changes in extracellular concentrations of serotonin in the anterior hypothalamus, striatum, and frontal cortex. After the onset of heatstroke, rats without brain serotonin depletion displayed hyperthermia, decreased mean arterial pressure, increased intracranial pressure, decreased cerebral perfusion pressure, decreased cerebral blood flow, increased cerebral serotonin release, and increased cerebral neuronal damage compared with those of normothermic control rats. However, when the cerebral serotonin system was destroyed by 5,7-dihydroxytryptamine, the heatstroke-induced arterial hypotension, intracranial hypertension, ischemic damage to the brain, and elevated cerebral serotonin release were reduced. In addition, the survival time of the heatstroke rats was prolonged after the depletion of brain serotonin. The data indicate that brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats.
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PMID:Brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats. 892 15

1. We examined monoamine contents in various regions of the brain and catecholamine contents in the heart and the adrenal gland of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats aged 1.5, 3 and 6 months. 2. The noradrenaline (NA) content and the 5-hydroxytryptamine (5-HT) content in the brainstem were larger in 1.5 month old SHRSP than in the age-matched WKY. In addition, at age 6 months the brainstem 5-HT content was higher in SHRSP than in WKY. 3. The NA and 5-HT contents in basal ganglia, thalamus, hypothalamus, septum and anterior and lateral cerebral cortex showed no significant difference between SHRSP and WKY at any age. 4. The dopamine (DA) contents in all brain regions examined did not differ between WKY and SHRSP at any age. 5. The NA contents in left and right ventricles were larger in 3 month old SHRSP than in the age-matched WKY, but were lower in 6 month old SHRSP than in the age-matched WKY. The cardiac DA contents did not differ between the two rat strains of any age. 6. The adrenal NA and adrenaline (A) contents in 6 month old SHRSP were significantly larger than those in the corresponding WKY. 7. These findings suggest that the increased NA and 5-HT contents in the brainstem may be related to the onset of hypertension, and that the altered cardiac NA contents and adrenal NA and A contents change as a result of the onset or persistence of hypertension.
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PMID:Age-related changes in cerebral and peripheral monoamine contents in stroke-prone spontaneously hypertensive rats. 907 53

Saiko-ka-ryukotsu-borei-to (TJ-12) is a Japanese kampo medicine used clinically for the treatment of hypertension and atherosclerosis. We investigated the effects of TJ-12 on the contraction of rat thoracic aorta induced by norepinephrine, 5-hydroxytryptamine and high potassium. TJ-12 relaxed endothelium-denuded rings, which had been precontracted with 1 microM norepinephrine, in a dose-dependent manner with an IC50 of 50 micrograms/mL. However, in the presence of TJ-12, endothelium-intact rings initially showed enhanced norepinephrine-induced contraction, followed by relaxation. Interestingly, TJ-12 dose-dependently reversed nitric oxide (2 microM)-induced relaxation of norepinephrine-induced precontraction ofendothelium-denuded rings, with an IC50 of 20 micrograms/mL. In serotonin-contracted rings, TJ-12 caused slight, though statistically significant, relaxation only at high doses (> 200 micrograms/mL). In constrat to these receptor-mediated contractions, TJ-12 failed to affect the tension produced by high potassium 40 mM). These results suggest that the antihypertensive effects of TJ-12 could be related to inhibition of norepinephrine-induced vasoconstriction. In addition, our in vitro experiments revealed an inhibitory effect on nitric oxide-induced relaxation.
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PMID:Endothelium-dependent and -independent vasoactive actions of a Japanese kampo medicine, Saiko-ka-ryukotsu-borei-to. 908 28

FR 173657, the first effective nonpeptide kinin B2 receptor antagonist, has been tested in four preparations from different species (human, pig, rabbit, and guinea pig). The new compound shows high apparent affinity for the four B2 receptors, with pA2 values ranging from 8.2 to 9.4 FR 173657 is a selective B2 receptor antagonist that does not interact with human, pig, or rabbit B1 receptors. The new compound is extremely specific for the kinin B2 receptors as it does not affect the myotropic effects of norepinephrine, endothelin-1, or 5-hydroxytryptamine in the human umbilical vein; the contractions elicited by substance P and angiotensin II in the rabbit jugular vein or those produced by acetylcholine and histamine in the guinea pig ileum; or the relaxation of the pig coronary artery induced by norepinephrine and substance P. FR 173657 acts as a competitive antagonist over an extended range of concentrations on human and rabbit B2 receptors, whereas on pig and guinea pig receptors, it depresses the maximal effect of bradykinin and thus appears to act as a noncompetitive antagonist.
Hypertension 1997 Apr
PMID:FR 173657: a new, potent, nonpeptide kinin B2 receptor antagonist. An in vitro study. 909 82

Dexfenfluramine increases serotonergic activity by stimulating serotonin (5-hydroxytryptamine; 5-HT) release into brain synapses, inhibiting its reuptake into presynaptic neurons and by directly stimulating postsynaptic serotonin receptors. On the basis of the serotonin hypothesis of appetite control, these actions would be expected to reduce appetite and, consequently, bodyweight. Studies conducted in animals and in overweight patients with and without associated disorders have confirmed the weight-reducing efficacy and good tolerability of dexfenfluramine. In 3-month clinical studies in obese patients, weight reductions with dexfenfluramine 15mg twice daily combined with dietary support were significantly higher than those achieved with placebo and similar to those with ephedrine/caffeine 20/20mg 3 times daily, sibutramine 10mg once daily and fluoxetine 60 mg/day. Furthermore, dexfenfluramine recipients with non-insulin-dependent diabetes mellitus, hyperlipidaemia or hypertension consistently show improvements in glycaemic control, blood lipid profiles and blood pressure. 12-month trial results indicate that most weight loss occurs in the initial 6 months and appears to be maintained for a further 6 months. Weight regain after withdrawal of treatment in 12-month studies demonstrates that dexfenfluramine is effective in maintaining a stable bodyweight at a lower level than placebo and in limiting food intake over this time period. Commonly reported adverse events with dexfenfluramine include diarrhoea, tiredness, dry mouth and somnolence; these symptoms are generally mild and transient. Approximately 7 and 10% of dexfenfluramine recipients in short and long term studies withdrew because of adverse events. Dexfenfluramine was better tolerated than ephedrine/caffeine and fluoxetine in short term studies. Obesity is a chronic condition that is accompanied by a number of metabolic complications. It is a significant health problem in developed countries, and as a major risk factor for many chronic diseases, including diabetes and cardiovascular disease, the economic burden of this condition is considerable. As with other chronic conditions, there is a role for pharmacological intervention in patients with severe obesity. However, drugs should be considered as only one component of a weight-control programme, since additional lifestyle modification is required to maintain weight loss. The promising data on the long term efficacy and tolerability of dexfenfluramine as well as its favourable effects on risk factors associated with obesity requires confirmation in long term studies. In the meantime, dexfenfluramine should be considered a valuable adjunct to a reduced-calorie diet in the management of severe obesity, particularly in patients with associated disorders and those unsuccessful with conventional weight loss measures. Available data support the use of the drug for up to 1 year to maintain weight loss and thus dexfenfluramine should be considered for long term administration.
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PMID:Dexfenfluramine. An updated review of its therapeutic use in the management of obesity. 911 19

We studied the effects of acute and chronic exercise on the arterial baroreflex and chemosensitive cardiopulmonary baroreflex (CCB) in spontaneously hypertensive rats (SHR). Arterial baroreflex and CCB were evaluated in normotensive rats (NR, n=11) and SHR (n=5) at rest and after 30 minutes of an acute bout of exercise (45 minutes at 50% of VO2max). In addition, these baroreflexes were evaluated in sedentary (n=5) and exercise-trained (n=9) SHR. Exercise training was performed on a motor treadmill, 5 days/week, during 60 minutes, at 50% of VO2max. Baroreflex bradycardia and tachycardia, analyzed by baroreflex sensitivity index (delta heart rate/delta mean arterial pressure), were significantly lower in SHR than in NR (0.7+/-0.1 versus 2.0+/-0.1 and 1.8+/-0.2 versus 3.4+/-0.1 beats per minute [bpm]/mm Hg, respectively). During the recovery period from acute exercise, baroreflex bradycardia was significantly higher than at rest only in SHR (1.7+/-0.1 versus 0.7+/-0.1 bpm/mm Hg). Hypotension and bradycardia induced by CCB stimulation (5-hydroxytryptamine, I.V.) were similar between SHR and NR, and an acute exercise bout did not change these responses. Exercise training markedly improved baroreflex bradycardia and tachycardia in SHR (1.9+/-0.1 versus 0.7+/-0.1 and 2.9+/-0.1 versus 1.8+/-0.2 bpm/mm Hg, respectively). Exercise-trained rats had greater bradycardiac (118+/-26 versus 14+/-2 and 209+/-30 versus 19+/-5 bpm to 1 and 2 microg/kg 5-HT, respectively) and hypotensive (30+/-6 versus 15+/-3 and 45+/-7 versus 17+/-2 mm Hg to 1 and 2 microg/kg 5-hydroxytryptamine, respectively) responses to CCB stimulation. In conclusion, an acute bout of exercise increases baroreflex bradycardia in SHR, and exercise training attenuates hypertension concomitant with improved arterial baroreflex and CCB sensitivity in SHR.
Hypertension 1997 Sep
PMID:Acute and chronic effects of exercise on baroreflexes in spontaneously hypertensive rats. 932 11

Insulin acutely decreases contractile agonist-induced Ca2+ influx and contraction in endothelium-free cultured vascular smooth muscle (VSM) cells, but the mechanism is not known. Since it has been reported that insulin-induced vasodilation in humans is linked to nitric oxide synthase activity, we wished to determine whether insulin inhibits Ca2+ influx and contraction of cultured vascular smooth muscle cells by a nitric oxide synthase-dependent pathway. Primary cultures of endothelial cell-free VSM cells from canine femoral artery were preincubated with and without 1 nmol/L insulin for 30 minutes, and the 5-minute production of cGMP was measured. Insulin alone did not affect cGMP production, but in the presence of 10(-5) mol/L serotonin insulin stimulated cGMP production by 60%. N(G)-monomethyl-L-arginine (0.1 mmol/L), an inhibitor of nitric oxide synthase, inhibited the conversion of arginine to citrulline by these cells, blocked insulin-stimulated cGMP production, and blocked the inhibition by insulin of 5-hydroxytryptamine (5-HT)-stimulated Mn+2 (a Ca2+ surrogate) influx and contraction. Insulin did not affect contraction of VSM cells grown under conditions designed to deplete the cells of tetrahydrobiopterin, an essential cofactor of nitric oxide synthase. These studies demonstrate that insulin acutely inhibits 5-HT-stimulated Ca2+ influx and contraction of endothelium-free cultured VSM cells by a nitric oxide synthase-dependent mechanism.
Hypertension 1997 Oct
PMID:Insulin acutely inhibits cultured vascular smooth muscle cell contraction by a nitric oxide synthase-dependent pathway. 933 95

Depression is a common, life-disrupting, potentially lethal illness that can affect both sexes and all ages. Its peak onset is in the early adult years. It is more common than hypertension in primary care practice. Recent studies show that fewer than 1 in 20 depressed patients are correctly diagnosed and adequately treated. Depression periodically destroys the productivity of those with the condition, and depressed patients have a worse quality of life than patients with debilitating, chronic conditions such as arthritis, hypertension, diabetes mellitus and back pain. Suicide occurs in as many as 15% of patients with depression, especially those with recurrent episodes and hospitalisations, and may even occur in those with in subsyndromal depression. Suicide is one of the leading causes of death, and individuals who complete suicide have usually experienced mood disorders, mainly depression. Current data support a decreased frequency of suicidal ideation with all antidepressants, including selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). Modern pharmacotherapy is the cornerstone for effective treatment of depression. As they are well tolerated, even in the presence of comorbid medical illness, and easier to manage, SSRIs enhance compliance. A fully adequate antidepressant dosage is suitable for patients of all ages and can be used by non-psychiatrist physicians for the treatment of the acute episode, as well as the frequent recurrences that often require long term maintenance antidepressant medication. SSRIs have fewer drug interactions than older antidepressants, and even the SSRI inhibition of hepatic cytochrome P450 enzymes has proven only very infrequently to be of clinical importance. SSRIs also effectively treat anxious depression, dysthymia and atypical depression. Fluoxetine may provide more rapid onset of therapeutic effect because it can be started at closer to its usual full therapeutic dosage than other SSRIs or older antidepressants. SSRIs, in particular fluoxetine, are more suitable for use as long-term maintenance therapy in these chronic relapsing diseases. These factors and the high efficacy rate, increased safety in overdose, reduced incidence of adverse effects (mostly decreasing with time) and superiority in ease of maintaining patients in adequate treatment plans provides fluoxetine with an overall superior therapeutic profile.
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PMID:Risks and benefits of selective serotonin reuptake inhibitors in the treatment of depression. 946 88


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