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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of peripheral serotonin receptor blockade on preeclamptic hypertension in 20 postpartum patients by the use of ketanserin, a serotonin receptor antagonist. In a study consisting of a double-blind crossover with placebo, parenteral ketanserin significantly reduced blood pressure from 167/105 to 126/71 mm Hg compared to a decline from 157/98 to 150/91 mm Hg for the placebo (p less than 0.001). All patients became hypertensive again following infusion, although no abrupt rebound in pressure occurred. Side effects were minimal. The results demonstrate that preeclamptic hypertension can be controlled by ketanserin and suggest that serotonin may have a role in the modulation of preeclampsia.
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PMID:Control of preeclamptic hypertension by ketanserin, a new serotonin receptor antagonist. 637 98

Ketanserin is a new, specific serotonin receptor blocking agent, which causes vasodilatation, presumably by an action on the vascular wall. The antihypertensive response to ketanserin 40 mg twice daily as monotherapy was assessed in 8 patients with essential hypertension. The investigation was an 8 week, double-blind, cross over study, which also included measurements during isometric (handgrip) and dynamic exercise (bicycle ergometry), as well as determination of plasma catecholamines and ketanserin. Ketanserin caused a reduction of supine and standing systolic and diastolic blood pressure (BP) during rest and a slight bradycardia. Although there was attenuation of the pressor response to handgrip, treatment with ketanserin did not really affect the changes in BP or heart rate during exercise, i.e. the base-line differences remained the same. There was no significant correlation between the effect on BP and the plasma level of ketanserin. The changes in BP produced by ketanserin showed little correlation with the initial levels of plasma catecholamines or with alterations in those levels. Although the results did not indicate direct interference by ketanserin with sympathetic tone, the lack of reflexogenic tachycardia, as well as the lack of increase in plasma noradrenaline during hand grip, indicates at least some modulation of autonomic function. It is concluded that ketanserin lowers BP in essential hypertension without interference with cardiovascular reflexes during standing or exercise, and that the compound may offer an alternative approach in the treatment of hypertension.
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PMID:Ketanserin in essential hypertension: effects during rest and exercise. 662 17

In anesthetized rats, electrical stimulation of pineal gland elicited proportional hypertension and tachycardia, which could be mimicked by microinjection of an excitatory amino acid, kainic acid (0.3 micrograms), into the pineal gland. The hypertension induced by pineal stimulation was antagonized by either spinal transection or postsynaptic blockade of serotonin receptors, while the tachycardia induced by pineal stimulation was antagonized by either serotonin receptor antagonism, bilateral vagotomy or spinal transection. In addition, postsynaptic blockade of serotonin receptors with cyproheptadine (2-5 mg/Kg, IV) produced both hypotension and bradycardia, while stimulation of 5-HT receptors with DOI (10-250 micrograms/Kg, IV) produced both hypertension and tachycardia in rats. The results indicate that pineal stimulation activates brain 5-HT receptors and results in sympathetic stimulation or parasympathetic inhibition which leads to hypertension and tachycardia in rats.
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PMID:Pineal stimulation produces both hypertension and tachycardia in rats. 818 91

Serotonin is a naturally occurring vasoactive substance that has diverse cardiophysiological effects. These effects can be explained by the existence of serotonin receptor subtypes which mediate different biological actions. The vasoconstrictive actions of serotonin are mediated by 5-HT2 serotonergic receptors, and serotonin also amplifies the release and activities of other vasoconstrictors, such as angiotensin and norepinephrine. Abnormalities in the serotonergic system may play an important role in the pathophysiology of multiple cardiovascular disease states such as systemic hypertension, primary pulmonary hypertension and peripheral vascular disease. Selective 5-HT2 serotonergic receptor blockers have been developed which appear to be potent vasodilators with therapeutic potential in various cardiovascular disease states. The largest clinical experience has been collected with ketanserin, and other agents in this class are being investigated. Prolongation of the ECG QT interval with 5-HT2 serotonergic receptor blockers may pose a potential risk with these treatments in some patients.
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PMID:Serotonin and the heart. 1082 27

The SHHF/Mcc-fa(cp) (spontaneous hypertension and heart failure) rat is advanced as a novel and suitable non-primate model of pregnancy-associated hypertension and fetal growth restriction because it simultaneously has spontaneous pregnancy-associated hypertension, small for gestational age (SGA) offsprings, and altered placental gene expression. Pregnancy-associated hypertension is a major contributor to maternal and fetal morbidity and mortality with the potential to result in maternal death and the need for iatrogenic preterm delivery. It has been reported to develop spontaneously in humans, but not in animals; consequently, progress in identifying the cause and pathogenesis of this disorder has been hampered. Spontaneous hypertension and heart failure rats develop hypertension spontaneously as they age, therefore we sought to determine whether these rats developed hypertension and SGA offsprings during pregnancy. Our results show that systolic blood pressure (BP) increased >40 mm Hg by the end of the first trimester and remained at this elevated level for the remainder of pregnancy, but decreased after parturition. Placenta weights of SHHF rats (0.60 +/- 0.02 g, n = 36) were significantly higher than Wistar-Kyoto (WKY) rats (0.42 +/- 0.01 g, n = 22, P < .05), but pup weights were significantly lower (2.68 +/- 0.06 g for SHHF rats compared to 3.24 +/- 0.06 g for WKY controls, P < .05). Histologic examination revealed pathologic lesions in neither heart, liver, placenta, nor kidney. L-Arginine administered in drinking water prevented the elevation of BP, particularly during the third trimester. Placentas from SHHF rats displayed altered expression of several genes whose protein products have been implicated in preeclampsia, including serotonin receptor, sodium channel, carbonic anhydrase, estrogen receptor regulator, major histocompatibility complex proteins, superoxide dismutase, and angiotensiogen. In addition, gene expression profiling showed alteration of a number of subcellular putative myristoylproteins not previously associated with preeclampsia, particularly those engaged in post-translational modifications in the placenta. Thus, SHHF rats may be a valuable tool, because it simultaneously has spontaneous pregnancy-associated hypertension, SGA offsprings, and altered placental gene expression.
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PMID:Spontaneous pregnancy-induced hypertension and intrauterine growth restriction in rats. 1171 Jul 86

Plasma prolactin (PRL) levels after acute administration of fenfluramine (FEN) have been used as a probe of brain serotonin activity. FEN-evoked increases in PRL levels inversely correlate with arterial blood pressure (ABP) in humans (Muldoon et al. Hypertension. 1998;32:972-975), thereby suggesting that brain serotonin activity may be reduced in hypertension. The present study sought to determine whether the relation between FEN-evoked PRL levels and ABP was present in two rat models of hypertension. Experiments were performed in awake male rats that were instrumented with femoral arterial and venous catheters 2 days before experiments. FEN (3.0 mg/kg IV) significantly increased plasma PRL levels in both spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY); however, FEN-evoked PRL levels were significantly lower in SHR compared with WKY, though baseline levels were similar between strains. Similar results were obtained in rats with chronic hypertension produced by figure-8 renal wrap plus contralateral nephrectomy. In contrast, the increase in PRL levels evoked by the serotonin receptor agonist m-CPP or the dopamine receptor antagonist eticlopride did not differ between SHR and WKY, indicating that PRL secretion is not generally blunted in chronic hypertensive rats. Furthermore, FEN-evoked PRL levels were not attenuated in rats made acutely hypertensive by an infusion of the alpha-adrenergic agonist phenylephrine. Thus, the present findings are consistent with the human data and suggest that chronic hypertension is associated with a presynaptic alteration in brain serotonin function.
Hypertension 2003 Oct
PMID:Blunted fenfluramine-evoked prolactin secretion in hypertensive rats. 1288 88

The carcinoid syndrome, associated with carcinoid tumors of the midgut, consists of symptoms such as diarrhea, flushing, wheezing and cardiovascular symptoms. This review focuses on these symptoms and discusses therapeutic options. The symptoms are caused by the secretion of biogenic amines, polypeptides and other factors of which serotonin is the most prominent. However, diarrhea is also due to factors such as malabsorption. Besides antitumor therapy, more specific interventions such as serotonin receptor blockers can be useful. The carcinoid heart disease involves the tricuspid and pulmonary valve. In the pathogenesis, serotonin plays a central role. The therapeutic approach is mostly symptomatic. Other cardiovascular complications include bowel ischemia and hypertension. Pellagra and psychiatric symptoms are due to a depletion of tryptophan, which is consumed by the carcinoid tumor for serotonin synthesis. Finally, follow-up and clinical practice of patients with carcinoid tumors are discussed.
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PMID:Complications of midgut carcinoid tumors and carcinoid syndrome. 1547 13

Worldwide, major depression is the leading cause of years lived with a disability, and the fourth cause of disability-adjusted life years. Depression is second only to hypertension as the most common chronic condition encountered in general medical practice. Unfortunately, despite the high prevalence of depression, under-recognition and under-treatment are common.Historically, clinicians have assessed the short-term effectiveness of antidepressants by response rates, often defined as a 50% reduction in depressive symptoms. However, this usually does not reflect true clinical remission, and residual symptoms are common. Persistence of residual symptoms appears to be a common link to relapse, chronic disability and suicide. The burden of not treating depression effectively to remission is significant, as the disease is an important contributor to the disability levels of the general population. Disability, in turn, has a profound impact on lost productivity and medical expenses. In 2000, depression cost the US more than US 83 billion dollars annually in lost productivity, medical expenses and premature death.Venlafaxine, a dual-acting serotonin norepinephrine (noradrenaline) reuptake inhibitor, may improve a patient's response to treatment and their chances of achieving complete remission compared with conventional antidepressant therapies, with the evidence for this being the strongest for comparisons with the selective serotonin receptor inhibitors (SSRIs). To date, there are only a small number of economic studies of venlafaxine, and most are cost or resource utilisation analyses with significant limitations. Nevertheless, two cost-effectiveness analyses of venlafaxine are available. They found venlafaxine had a lower average cost per patient achieving remission or per symptom-free day compared with SSRIs; one reported an incremental cost-effectiveness ratio for venlafaxine of US 586 dollars (year 2002 values) per additional patient achieving remission over 8 weeks, and the other found venlafaxine to be a dominant treatment choice over SSRIs over 6 months (year 2001 values). Although requiring further confirmation, these initial data suggest that venlafaxine is a cost-effective strategy for the treatment of depression. The availability of an effective armamentarium of antidepressant strategies, including venlafaxine, to achieve and sustain remission offers both clinical and economic value to all those touched by the burden of depression.
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PMID:Remission from depression : a review of venlafaxine clinical and economic evidence. 1596 May 53

Pulmonary arterial vasoconstriction is an important early component of pulmonary hypertension. Inflammatory mechanisms play a prominent role in the pathogenesis of pulmonary hypertension. The present authors investigated the potential role of acute allergic lung inflammation for alterations in pulmonary haemodynamics. BALB/c mice were intraperitoneally sensitised to ovalbumin and challenged by ovalbumin inhalation. Subsequently, lungs were ventilated and perfused ex vivo, and pulmonary arterial pressure (P(pa)) was continuously monitored. Isolated perfused lungs of allergen-sensitised and -challenged mice showed five-fold enhanced P(pa) responses to serotonin, which is reported to be a significant contributor to pulmonary hypertension in humans. This increase in P(pa) was abolished by the serotonin receptor-2A antagonist ketanserin, but not the serotonin receptor-1B antagonist GR127935. Intracellular signalling to serotonin involved phosphatidylcholine-specific phospholipase C and protein kinase C, as well as Rho-kinase, as assessed by employing the specific inhibitors D609, bisindolylmaleimide and Y27632, respectively. In addition to serotonin, impressively enhanced P(pa) increases in allergic lungs were also evoked by the thromboxane receptor agonist U46619, angiotensin II and endothelin-1. In conclusion, allergic lung inflammation was accompanied by impressive pulmonary vascular hyperresponsiveness. These results suggest a possible role for allergic inflammation in the development of pulmonary arterial hypertension.
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PMID:Allergic lung inflammation induces pulmonary vascular hyperresponsiveness. 1657 13

We report a 16-year-old man with severe heart failure due to idiopathic pulmonary arterial hypertension (IPAH). The patient was initially treated with a combination of beraprost, a prostacyclin analog, and sarpogrelate, a serotonin receptor inhibitor. However, he was unresponsive to the treatment. We then changed the treatment to sildenafil, and his condition dramatically improved. Sildenafil has an immediate pulmonary vasodilator effect in patients already receiving vasodilators for IPAH.
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PMID:Marked improvement with sildenafil in a patient with idiopathic pulmonary arterial hypertension unresponsive to beraprost and sarpogrelate. 1757 85


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