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

A two week administration of the glucocorticoid betametasone to male Wistar rats produced a mild hypertensive state. The brain of these rats showed some significant changes in amine and metabolite content with respect to normotensive controls. Epinephrine and metanephrine were increased in the rostral ventrolateral medulla and in the preoptic area. Epinephrine also increased in the septal area. Normetanephrine decreased in the rostral ventrolateral medulla. Dopamine and homovanillic acid increased in septal and preoptic areas. Dopamine alone increased in rostral ventrolateral medulla. Serotonin and 5-hydroxyindole-3-acetic acid increased in the septal area and dorsal medulla. These changes suggest significant alterations in the aminergic activity of the brain circuitry known to regulate cardiovascular functions; the changes may play a basic role in the development and maintenance of glucocorticoid-induced hypertension.
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PMID:Brain amines in glucocorticoid-induced hypertension in the rat. 162 93

Dopamine is an endogenous catecholamine that modulates many functions including behavior, movement, nerve conduction, hormone synthesis and release, blood pressure, and ion fluxes. Dopamine receptors in the brain have been classically divided into D1 and D2 subtypes, based on pharmacological data. However, molecular biology techniques have identified many more dopamine receptor subtypes. Several of the receptors cloned from the brain correspond to the classically described D1 and D2 receptors. Several D1 receptor subtypes have been cloned (D1A, D1B, and D5) and are each coupled to the stimulation of adenylyl cyclase. The D2 receptor has two isoforms, a shorter form, composed of 415 amino acids, is termed the D2short receptor. The long form, called the D2long receptor, is composed of 444 amino acids; both are coupled to the inhibition of adenylyl cyclase. The D3 and D4 receptors are closely related to, but clearly distinct from, the D2 receptor. They have not yet been linked to adenylyl cyclase activity. Outside of the central nervous system, the peripheral dopamine receptors have been classified into the DA1 and DA2 subtypes, on the basis of synaptic localization. The pharmacological properties of DA1 receptors roughly approximate those of D1 and D5 receptors, whereas those of DA2 receptors approximate those of D2 receptors. A renal dopamine receptor with some pharmacological features of the D2 receptor but not linked to adenylyl cyclase has been described in the renal cortex and inner medulla. In the inner medulla, this D2-like receptor, termed DA2k, is linked to stimulation of prostaglandin E2 production, apparently due to stimulation of phospholipase A2. Of the cloned dopamine receptors, only the mRNA of the D3 receptor has been reported in the kidney. The DA1 receptor in the kidney is associated with renal vasodilation and an increase in electrolyte excretion. The DA1-related vasodilation and inhibition of electrolyte transport is mediated by cAMP. The role of renal DA2 receptors remains to be clarified. Although DA1 and DA2 receptors may act in concert to decrease transport in the renal proximal convoluted tubule, the overall function of DA2 receptors may be actually the opposite of those noted for DA1 receptors. Dopamine has been postulated to act as an intrarenal natriuretic hormone. Moreover, an aberrant renal dopaminergic system may play a role in the pathogenesis of some forms of hypertension. A decreased renal production of dopamine and/or a defective transduction of the dopamine signal is/are present in some animal models of experimental hypertension as well as in some forms of human essential hypertension.
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PMID:The renal dopamine receptors. 162 51

Dopamine beta-hydroxylase (DBH) deficiency is a genetic disorder in which affected patients cannot synthesize norepinephrine, epinephrine, and octopamine in either the central nervous system or the peripheral autonomic neurons. Dopamine acts as a false neurotransmitter in their noradrenergic neurons. Neonates with DBH deficiency have had episodic hypothermia, hypoglycemia, and hypotension, but survivors sometimes cope relatively well until late childhood when overwhelming orthostatic hypotension profoundly limits their activities. The hypotension may be so severe that clonic seizures supervene. Most currently recognized patients are young or middle-aged adults. The diagnosis is established by the observation of severe orthostatic hypotension in a patient whose plasma norepinephrine/dopamine ratio is much less than one.
Hypertension 1991 Jul
PMID:Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. 167 40

Dopamine receptors of DA-1 and DA-2 subtypes are localized in various regions within the kidney including the renal vasculature (DA-1) as well as sympathetic nerve terminals innervating the renal blood vessels (DA-2). More recent studies using receptor-ligand binding and receptor autoradiography have shown that DA-1 receptors are localized at both the luminal and basolateral membranes at the level of the proximal tubules. Activation of these DA-1 receptors by dopamine and by selective DA-1 receptor agonists results in natriuresis and diuresis. The cellular signaling mechanisms responsible for this response appear to be DA-1 receptor-induced activation of adenylate cyclase and phospholipase C, which via the generation of various intracellular messenger systems cause inhibition of Na(+)-H+ antiport (luminal) and Na+, K(+)-ATPase (basolateral), respectively. Both of these events consequently inhibit sodium reabsorption leading to natriuresis and diuresis. It is also known that dopamine can be synthesized within proximal tubular cells from L-dopa, which is taken up from the tubular lumen, and this locally produced dopamine plays an important role in the regulation of sodium excretion particularly during increases in sodium intake. Furthermore, a defect in the renal dopaminergic mechanism may be one of the pathogenic factors in certain forms of hypertension. Finally, whereas DA-1 receptor agonists are shown to be of therapeutic benefit in the treatment of hypertension, heart failure, and acute renal failure, some selective DA-2 receptor agonists are effective antihypertensive agents.
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PMID:Anatomical distribution and function of dopamine receptors in the kidney. 168 44

Dopamine, an ancestral catecholamine, is physiologically natriuretic and vasodilating, thus essentially protecting against hypertension. Its actions are overshadowed by the opposite effects of its main biological partner, norepinephrine, and this is accentuated with aging. Clinical observations combined with molecular biology approaches to catecholamine-synthesizing and catecholamine-metabolizing enzymes and receptors permit the identification of some inborn defects. Subtle changes in the dopamine-norepinephrine balance may account for the enhanced peripheral noradrenergic activity seen in the setting of decreased dopaminergic activity in advanced age. These changes may contribute to the diminished ability of the aged kidney to excrete a salt load, as well as to the finding that systolic blood pressure increases with age in populations with a high, but not in those with a low, intake of salt. The attainment of advanced age in Western societies with adverse lifestyle changes (mental rather than physical stress, excess salt intake, overeating, sedentarism) appears to facilitate the development of hypertension. The adaptation to all the preceding lifestyle changes necessitates an increased dopamine generation, which may initially compensate to maintain appropriate natriuresis and vasodilation since many patients with initial borderline essential hypertension express their sympathetic hyperfunction, in addition to increased norepinephrine release, by excessive dopamine release. However, the progression of hypertension is accompanied by a peripheral dopaminergic deficiency and diminished ability to excrete salt. This may represent an eventual inadequacy of a phylogenetically redundant system resulting in decreased natriuresis and vasodilation and may account for the responsiveness of established chronic hypertension to salt restriction, diuretics, and dopaminomimetic medication.
Hypertension 1991 Dec
PMID:Peripheral dopamine in pathophysiology of hypertension. Interaction with aging and lifestyle. 168 57

We measured daily urinary excretion rates of dopamine and dopa during dietary salt loading and natriuretic responses to exogenous dopamine in Dahl salt-sensitive (DS), Dahl salt-resistant (DR) and Sprague-Dawley rats. Excretion rates of dopa increased approximately sixfold during salt loading in all rat strains. Maximal urinary dopa responses were attained within 1 day of salt loading. Daily excretion rates of dopamine also increased about five- to sixfold in DS and DR rats and about twofold in Sprague-Dawley rats, with maximal dopamine responses attained by day 5. Dopamine infusion (3 micrograms/kg per min) increased urinary sodium excretion by 406 +/- 132 % (mean +/- s.e.m.) in Sprague-Dawley rats but only 267 +/- 131% and 147 +/- 80% in DS and DR rats (P less than 0.05 for Sprague-Dawley versus Dahl rats). The results demonstrate that salt loading markedly and rapidly increases dopa excretion in rats. Considering values for dopamine excretion in other rat strains, the results suggest that Dahl rats have increased formation of dopamine for a given amount of dopa delivery to the kidney and that this abnormality is unrelated to salt-sensitive hypertension in DS rats. The results also provide in vivo support for the view that the responsiveness of renal dopamine receptors mediating natriuresis is related to production of endogenous dopamine in the kidney.
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PMID:Endogenous dopa and dopamine responses to dietary salt loading in salt-sensitive rats. 185 89

High performance liquid chromatography (HPLC) with electrochemical detection proves to be a reliable method for determination of plasma catecholamines (CA) to assess the possible role of the sympathetic nervous system (SNS) in essential hypertension (EH). The present investigation in a group of 15 normotensive (N) and 13 stable EH patients, homogeneous for age and duration of hypertension, was carried out without treatment in the supine position, up-right position and during a personalized bicycle exercise. Mean blood pressure, mean heart rate, plasma renin activity and plasma aldosterone were also evaluated at the various exertion phases. Norepinephrine (NE) and epinephrine (E) showed a progressive increase in N and in EH patients, reaching the highest values at maximum effort. However, EH patients showed higher E plasma levels than N before maximum effort. Dopamine (DA) reached the highest values in N at maximum effort and in EH patients at recovery time. These findings allow us to foresee the possibility of a better characterization of the SNS role in EH.
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PMID:Plasma catecholamine responses during a personalized physical stress as a dynamic characterization of essential hypertension. 188 70

Dopamine in urine is derived substantially from renal uptake and decarboxylation of 3,4-dihydroxyphenylalanine (dopa), and increases in excretion of dopa normally parallel increases in excretion of dopamine during salt loading. Since patients with salt-sensitive hypertension may have decreased urinary excretion of dopamine during dietary salt loading, the present study was designed to evaluate the response of dopa to salt loading. Sixteen inpatients with normal-renin essential hypertension ate a constant metabolic diet containing 9 mmol/day sodium for 7 days, followed by the same diet but containing 249 mmol/day sodium for 7 days. Salt sensitivity was defined as an increase in mean arterial pressure of 8 mm Hg between the diets; on this basis, nine patients were salt-sensitive and seven, salt-resistant. The rate of urinary dopa excretion was significantly higher in the salt-sensitive patients throughout the study (mean rates 132 +/- 13 nmol/day in the salt-sensitive group and 78 +/- 9 nmol/day in the salt-resistant group for the 14 days of observation, p less than 0.01). When dietary sodium intake was increased to 249 mmol/day, urinary dopa excretion increased significantly more in salt-sensitive patients than salt-resistant patients. At the end of the high salt diet, dopamine excretion was significantly attenuated in the salt-sensitive patients, despite higher rates of dopa excretion. Thus, the urinary ratio of dopamine to dopa was decreased in salt-sensitive patients, regardless of salt intake.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Nov
PMID:High urinary dopa and low urinary dopamine-to-dopa ratio in salt-sensitive hypertension. 193 64

Dopamine (DA)--previously regarded simply as the precursor of norepinephrine--is now known to have its own unique effects on cardiovascular regulation which are mediated, in part, by activating specific DA receptors. DA has long been used in the treatment of shock and heart failure. In recent years it has been used at low infusion rates for its renal effects, in combination with other more specific inotropic or pressor agents. Lack of oral bioavailability has limited its use in long-term therapy, however; levodopa and dopa conjugates which are orally absorbed and metabolized to the active form are under investigation. The novel DA1 receptor agonist fenoldopam is claiming a role in the management of hypertension, heart failure, and the preservation of renal function. DA2 receptor agonists are also being evaluated as potential antihypertensive agents.
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PMID:Dopamine and dopamine receptor agonists in cardiovascular therapy. 196 61

Dopamine-1 (DA1) receptors in the renal tubules may be involved in the regulation of sodium homeostasis. To test this hypothesis, fenoldopam, a selective DA1 agonist, was infused at 0.05 microgram/kg/min i.v. in 16 normal male subjects in metabolic balance at 300 or 10 meq sodium. Renal function studies were performed by standard p-aminohippurate, inulin, and lithium clearances for three periods: 1) precontrol (2 hours), 2) experimental (3 hours), and 3) postcontrol (2 hours). DA1 receptor stimulation in sodium-loaded individuals increased the following parameters during the experimental period: urine flow rate, from 12.5 +/- 0.4 to 15.5 +/- 0.5 ml/min (p less than 0.05); urinary sodium excretion, from 309 +/- 12 to 489 +/- 18 mu eq/min (p less than 0.001); renal plasma flow, from 631 +/- 19 to 717 +/- 21 ml/min (p less than 0.005); fractional sodium excretion, from 2.2 +/- 0.1% to 3.4 +/- 0.1% (p less than 0.001); fractional lithium excretion, from 26.2 +/- 0.7% to 32.1 +/- 0.8% (p less than 0.005); and distal sodium load, from 10.7 +/- 0.4 to 13.8 +/- 0.5 ml/min (p less than 0.05). The increase in fractional sodium excretion was greater than that of fractional lithium excretion (p less than 0.0001). Distal sodium reabsorption decreased from 78.3 +/- 0.8% to 73.2 +/- 1.1% but the change was not statistically significant. In contrast, sodium-depleted subjects exhibited no significant changes except in renal plasma flow, which rose from 550 +/- 13 to 625 +/- 17 ml/min (p less than 0.0001). Glomerular filtration rate remained unchanged through the entire study. These results indicate that diuretic and natriuretic responses are mediated by DA1 receptors at both proximal and distal tubular sites. Attenuation of the DA1 natriuretic response during sodium depletion suggests a direct inhibition of cellular DA1 mechanisms in the renal tubule or recruitment of nondopaminergic compensatory homeostatic mechanisms within the kidney.
Hypertension 1990 Jun
PMID:Selective peripheral dopamine-1 receptor stimulation. Differential responses to sodium loading and depletion in humans. 197 40


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