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

The possible role of 5-hydroxytryptamine (serotonin) in patients developing hypertension following coronary artery bypass surgery was investigated by intravenous administration of ketanserin, a specific 5-hydroxytryptamine-receptor antagonist. Our findings in the preliminary study indicate that 5-hydroxytryptamine might not play a role in the hypertension seen after coronary artery bypass surgery.
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PMID:Ketanserin in the treatment of hypertension following coronary artery bypass surgery. A preliminary study. 660 47

Intraspinal (i.s.) injection of 6-hydroxydopamine or 5,7-dihydroxytryptamine in newborn spontaneously hypertensive rats (SHR) resulted, in the adult animal (30-week-old), in a marked decrease of spinal cord noradrenaline (NA) or 5-hydroxytryptamine (5-HT) levels, respectively. Since both neurotoxin- and vehicle-injected rats developed full hypertension and had similar plasma catecholamine concentrations, it is concluded that in SHR neither spinal cord NA nor 5-HT play a major role in development and maintenance of hypertension.
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PMID:Effects of neurochemical lesions restricted to spinal cord monoaminergic neurons on blood pressure and sympathetic activity of spontaneously hypertensive rats. 661 19

The release of 5-hydroxytryptamine (5-HT) from aggregating platelets may trigger acute vasospastic episodes of larger arteries, which can lead to tissue ischemia, particularly in the coronary and cerebral circulations. In hypertensive humans and animals, 5-HT may play a role in the maintenance of the chronic increase in peripheral resistance. This is suggested by the observations that 1) in several models of chronic hypertension there is a specific increase in the responsiveness of the blood vessel wall to the vasoconstrictor properties of 5-HT and a delayed tachyphylaxis to the monoamine; 2) the ability of hypertensive animals to clear 5-HT from the blood is reduced, and the platelets of hypertensive patients take up less 5-HT than those of normotensive humans; their activation to release 5-HT is accelerated; and 3) ketanserin, a 5-HT2-serotonergic antagonist devoid of agonistic properties, lowers arterial blood pressure in hypertensive humans and animals.
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PMID:5-hydroxytryptamine and vascular disease. 682 94

To see whether the increased peripheral vascular resistance seen in human hypertension is due to an altered reactivity of vascular smooth muscle, strips of digital arteries obtained post mortem from 13 hypertensive have been compared with those from 13 normotensives. The strips from the hypertensives were significantly thicker than those from the normotensives, as were those from male patients compared to females. This was reflected in a significantly greater response of the strips from the hypertensives and males to 80 mM KCl. The maximum responses to noradrenaline and 5-hydroxytryptamine, but not the concentrations required to produce 50% of the maximum responses, were significantly smaller in the strips from hypertensives than in those from normotensives. There were no significant differences between the strips from hypertensives and normotensives in either the maximum responses to angiotensin or barium chloride, or the concentration of those agonists required to produce 50% of the maximum response. It is concluded that the decreased reactivity to noradrenaline of the hypertensive vessels may be a sequel of either the increased pressure itself or increased exposure in vivo of the blood vessels from hypertensives to noradrenaline.
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PMID:Reactivity of isolated digital arteries in hypertension. 694 35

The renal resistance vessels of the mature spontaneously hypertensive rat (SHR) exhibit increased reactivity to vasoconstrictor agonists. This could be a cause or consequence of hypertension. We have compared vascular reactivity in isolated perfused kidneys from 46-day-old SHR and from normotensive control rats. The amplitude of responses in kidneys from the SHR to angiotensin II, barium chloride, or norepinephrine was not different from the control. Therefore, increased reactivity of the renal vascular smooth muscle cannot be an early pathogenic mechanism in spontaneous hypertension. Responses evoked by 5-hydroxytryptamine (serotonin) were of a greater amplitude in the SHR than in the control kidney. However, this difference was due to an interaction of serotonin with the sympathetic nerves, as it was abolished by treatment of the rats with 6-hydroxydopamine. Responses induced by electrical stimulation of the renal sympathetic nerves were also of greater amplitude in SHR than in control kidneys, both before and after the blockade of norepinephrine disposition mechanisms. Nerve stimulation evoked a greater efflux of endogenous norepinephrine from kidneys of the SHR than from those of control rats. Thus, the increased reactivity of the SHR kidney to renal nerve stimulation is due to an augmented release of endogenous norepinephrine. This could be an important factor in the early development of hypertension.
Hypertension
PMID:Renal vascular reactivity in the young spontaneously hypertensive rat. 696 55

The isolated and perfused kidney of the mature spontaneously hypertensive rat (SHR) exhibits an increased vascular reactivity and a delayed tachyphylaxis to 5-hydroxytryptamine, when compared to weight-matched normotensive animals. To evaluate the influence of the duration of the hypertensive state on these differences, the vascular reactivity to 5-hydroxytryptamine was determined in isolated kidneys from age-matched normotensive and spontaneously hypertensive rats of 3.5, 6 and 12 months of age. Responses to increasing doses of 5-hydroxytryptamine were compared. At all ages the responses to the agonist were greater in the SHR than in the control rats. In the normotensive rats, the sensitivity to the monoamine decreased, while the maximal response increased with aging. The vascular reactivity to increasing doses of 5-hydroxytryptamine was not altered by aging in the SHR. There was a significant correlation between the maximal vasoconstrictor response to 5-hydroxytryptamine in the isolated kidneys and the systolic arterial blood pressure (SBP) of the donor rats. Maximal constrictor responses to 5-hydroxytryptamine were repeated at given intervals. The degree of tachyphylaxis was decreased in hypertensive rats compared with normotensive rats at 3.5, and 6 months age. Tachyphylaxis to 5-hydroxytryptamine was depressed by aging in both normotensive and hypertensive rats. By contrast, tachyphylaxis to angiotensin II (AII) was not effected by either age or hypertension. There was no cross-tachyphylaxis between 5-hydroxytryptamine and AII. Lowering the Ca2+-concentration of the perfusate did not affect tachyphylaxis to either 5-hydroxytryptamine or AII. The present experiments indicate that the delayed tachyphylaxis to 5-hydroxytryptamine in the kidneys of SHR is due to a specific alteration of th vascular smooth muscle cells, which may be the consequence of premature aging.
Hypertension
PMID:Effect of age and spontaneous hypertension on the tachyphylaxis to 5-hydroxytryptamine and angiotensin II in the isolated rat kidney. 729 25

Vascular responsiveness to 5-hydroxytryptamine (5-HT) is dramatically increased in hypertension. The hypothesis that augmented vasoconstriction to 5-HT in hypertension is due to a change in receptor subtype on vascular myocytes was tested. Mesenteric arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive (systolic blood pressure > 180 mm Hg) and sham normotensive (systolic blood pressure < 130 mm Hg) rats were mounted in isolated tissue baths for measurement of isometric contractile force. The receptor mediating contraction in isolated mesenteric arteries from sham and DOCA-salt hypertensive rats is a member of the 5-HT2 family based on rank order of agonist potency (5-HT = alpha-methyl-5-HT [5-HT2 receptor agonist]>tryptamine>5-hydroxykynuramine). 5-HT was approximately 10-fold more potent in contracting mesenteric arteries from DOCA-salt hypertensive rats compared with arteries from sham normotensive rats. The tryptophan metabolite kynuramine, which possesses significant contractile activity at the 5-HT2B receptor, contracted hypertensive arteries significantly (50% of 5-HT maximum) but not sham arteries. Ketanserin (5-HT2A antagonist) competitively inhibited contraction to 5-HT in arteries from normotensive rats (-log dissociation constant [mol/L]; pKB = 8.54) but not from hypertensive rats (pKB > 6.5). Moreover, contraction to kynuramine was not blocked by ketanserin. Thus, under normal conditions, 5-HT2A receptors mediate contraction to 5-HT. However, in DOCA-salt hypertension, ketanserin-insensitive 5-HT2 receptors, possibly 5-HT2B receptors, mediate mesenteric arterial contraction to 5-HT.
Hypertension 1995 Dec
PMID:5-Hydroxytryptamine2B receptor mediates contraction in the mesenteric artery of mineralocorticoid hypertensive rats. 749 67

Chronic hypertension is associated with impaired endothelial function [i.e., reduced synthesis/release of endothelium-derived relaxing factor (EDRF) and increased synthesis/release of endothelium-derived contracting factor (EDCF)] in both animals and humans. Although it is not known whether endothelial dysfunction is the consequence and/or an important pathogenetic cause of hypertension, the goal of effective antihypertensive therapy should include restoration of normal endothelial function as well. Because angiotensin I-converting enzyme (ACE) inhibitors are effectively used in the treatment of hypertension, the aim of the present study was to test whether in vivo treatment of spontaneously hypertensive rats (SHRs) with the ACE inhibitor cilazapril improves endothelial function in the isolated thoracic aorta of SHRs. Treatment of SHRs with cilazapril (10 mg/kg/day orally for 2 weeks) resulted in a significant decrease in blood pressure and normalization of endothelium-dependent relaxation evoked by acetylcholine (ACh) and adenosine diphosphate (ADP). However, cilazapril treatment had no significant effect on endothelium-dependent contractions evoked by 5-hydroxytryptamine (5-HT; serotonin) and prostaglandin F2 alpha (PGF2 alpha). In contrast, in vitro treatment of isolated thoracic aortas with indomethacin (10(-5) M) normalized endothelium-dependent relaxations to ACh and ADP as well as inhibited endothelium-dependent contractions to 5-HT and PGF2 alpha. These results suggest that the ACE inhibitor cilazapril increases the synthesis/release of EDRFs whereas indomethacin prevents the synthesis/release of cyclo-oxygenase-derived EDCFs in the endothelium of rat aorta. The exact mechanism of action of ACE inhibitors on endothelial dysfunction remains to be determined.
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PMID:Effect of cilazapril and indomethacin on endothelial dysfunction in the aortas of spontaneously hypertensive rats. 750 48

Normal aging is associated with different changes in the cardiovascular system that lead to an increase in pathological processes, such as hypertension, coronary artery disease, heart failure, and postural hypotension with enhancement of both morbidity and mortality. The vascular alterations consist of changes in the function and structure of the arteries, and increasing vascular stiffness, mainly when atherosclerosis is present, whose incidence is increased with age. The arteries accumulate lipids, collagen, and minerals. Cerebral perfusion may be reduced in the elderly, mainly regional cerebral blood flow, which leads to a deterioration of mental and physical functions. The degree of deterioration is increased when aging is associated with hypertension. Aging alters endothelial cells, which play an important role in vascular tone regulation. Such a process tends to reduce endothelium-dependent relaxations, and clearly reduces the vasodilation elicited by beta-adrenoceptor agonists. The contractions induced by different agents, such as 5-hydroxytryptamine, histamine, high potassium and angiotensin are barely affected with aging, whereas those elicited by noradrenaline or endothelin are usually reduced. However, plasma noradrenaline levels are increased with age, mainly due to a reduction in the sensitivity of presynaptic alpha 2-adrenoceptors and also of noradrenaline uptake. Sodium pump activity, that controls cellular ionic homeostasis, may be altered depending on animal species. Finally, vascular Ca2+ regulation appears to be altered and the extracellular Ca2+ dependence of contractile responses elicited by agonists is increased, which justifies the enhanced sensitivity to Ca2+ antagonists in senescence.
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PMID:Age-related changes in vascular responses: a review. 761 68

Autonomic dysreflexia (AD) is a clinical phenomenon that affects patients with spinal cord injury (SCI) above the major sympathetic outflow tract. The lesion is most often at or above the T-6 level. Any noxious stimuli below this level initiate reflex sympathetic activity resulting in life threatening hypertension uncontrollable by the feedback parasympathetic activity. The episodes of hypertension generally persist until the offending stimulus is removed. Absence of higher control over reflex sympathetic activity due to transection of the cord is an anatomical explanation of the phenomenon. Current evidence suggests additional factors such as supersensitivity and possibly increased numbers of spinal alpha adrenoreceptors and peripheral microvascular adrenoreceptors as well as accumulation of substance P below the lesion. It has been suggested that substance P acts as a modulator, initiating the sympathetic event to produce a strong, slow and prolonged excitatory action. Autonomic dysreflexia is further accentuated by the absence of gamma amino benzoic acid (GABA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT) below the lesion. GABA is an inhibitory neurotransmitter. It has been suggested that either NE or 5-HT may also act as an inhibitory neurotransmitter. Resetting of the baroreceptors at a lower level also plays an important role. The anatomical transection at or above T-6 then helps in maintaining and accentuating the biochemical changes that develop in patients with high spinal cord lesions. The current article reviews the pathophysiology and management of this potentially life threatening, yet easily treatable, phenomenon.
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PMID:Autonomic dysreflexia revisited. 764 Sep 77


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