Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A hypothalamic role in the aetiology of hypertension in the spontaneously hypertensive rat (SHR) has been suggested by prior observations. In an attempt to determine whether the central control of prolactin (PRL) release is altered in the SHR we have compared the PRL response to immobilization stress, thyrotrophin releasing hormone (TRH), haloperidol, and L-DOPA in the SHR and in normotensive Wistar control rats. Carotid artery catheters were inserted 48 h prior to the PRL response studies and the catheters were maintained patent with heparinized saline. Timed blood samples were obtained in SHR and control rats weighing 180-225 g. The SHR demonstrated elevated basal serum levels of PRL and greater PRL responses to stress. However, administration of L-DOPA resulted in a similar suppression of serum PRL in the SHR and in the normotensive controls. These findings suggest alteration in the central control of PRL release in the SHR. Observations of elevated basal PRL, exaggerated PRL in response to L-DOPA in SHR are consistent with normal pituitary responsiveness to dopamine suppression of PRL release, but defective hypothalamic metabolism of dopamine. Alterations in central dopamine control mechanisms in the SHR may play a role in the pathogenesis of essential hypertension in these animals.
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PMID:Hyperprolactinaemia in the spontaneously hypertensive rat. 10 13

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)
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PMID:High urinary dopa and low urinary dopamine-to-dopa ratio in salt-sensitive hypertension. 193 64

In order to clarify the role of renal dopaminergic activity in renal sodium-water metabolism, the effects of oral administration of L-DOPA (400 mg), were studied on blood pressure (BP), plasma renin activity (PRA), plasma aldosterone concentration (PAC), urinary volume (UV), urinary excretion of sodium and lithium (UNa and ULi) in 11 normal subjects (N) and 32 patients with essential hypertension (EH). EH were divided into the salt sensitive (SS) and non salt-sensitive (NSS) groups by response of mean blood pressure (10% increase) after administration of NaCl. The change of UNa, PRA, and PAC after administration of NaCl were lower in SS than in NSS. After administration of L-DOPA, BP falled and UV, UNa, FENa, FELi and Ccr increased in both N and EH. The change of these factors were greater in SS as compared with those in NSS. These results suggest that in SS patients the suppression of water-sodium handling in the kidney might be due to depression of renal dopaminergic activity. Renal dopaminergic activity may play an important role in the pathogenesis of EH.
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PMID:[Significance of renal dopamine on pathogenesis of essential hypertension]. 206 17

Although plasma levels of L-dopa are derived substantially from catecholamine-synthesizing tissues, melanocytes--which produce L-dopa as part of the melanin synthetic cascade--also may be a source of circulating L-dopa. We compared plasma L-dopa levels in albino subjects and in Caucasian and Black normal volunteers and patients with essential hypertension. DOPA levels were similar among the subject groups. Among Caucasian normal volunteers, L-dopa levels were negatively correlated with subject age (r = -0.30, P less than 0.05), whereas norepinephrine levels tended to increase with subject age (r = 0.25, 0.05 less than P less than 0.10), so that the L-dopa:norepinephrine ratio was highly negatively correlated with subject age (r = -0.50, P less than 0.01). Skin pigmentation does not contribute importantly to plasma L-dopa levels in humans. In contrast with levels of norepinephrine, L-dopa levels appear to decrease during normal aging.
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PMID:Skin color, aging, and plasma L-dopa levels. 275 81

Basal excretion of DOPA, dopamine, noradrenaline and adrenalin and its variation in response to oral administration of L-DOPA, a catecholamine precursor, were measured in 491 patients with essential hypertension, cardiomyopathy and myocardial infarction to assess catecholamine synthesis reserves at the systemic level. It is suggested that the development and progress of these diseases is associated with initial activation of the system, accompanied by increased noradrenaline release, which is followed by a gradual decrease in mediator synthesis reserves. The physiologic noradrenaline/adrenalin constant hypothesis, based on clinical and experimental evidence, is supported by the results of catecholamine studies in the heart and the central nervous system in cases of sudden human cardiac death, demonstrating an abrupt drop in noradrenaline. A conclusion is made that adaptive-trophic adrenosympathetic function is linked with biochemical events maintaining noradrenaline content within a normal range.
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PMID:[The heart and catecholamines from the viewpoint of the adaptive-trophic function of the sympathetico-adrenal system]. 314 48

We report a reliable method for determining DOPA levels in plasma and cerebrospinal fluid. The method is based on complete conversion of DOPA to dopamine and quantification by HPLC-ECD of the dopamine formed. Lower limit of detection was 0.5 nmol/l. No differences in plasma DOPA levels were found between normal children (0-15 yr, n = 60), normal adults (n = 39) and patients with essential hypertension (n = 40) or Parkinson's disease (no DOPA therapy, n = 30). In normal individuals and in patients with essential hypertension venous plasma levels were higher than arterial levels (10.2 vs 9.3 nmol/l, p less than 0.001, V/A ratio 1.11 (SD 0.08), n = 15). Sympathetic stimuli (standing, tilting, bicycle exercise, tyramine) did not influence DOPA levels. In untreated depressed patients (n = 10) and in non-parkinsonian neurological patients (n = 12) cerebrospinal fluid levels of DOPA were 4.5 (SD 2.4) and 5.2 (SD 1.3) nmol/l respectively. A direct method for the measurement of DOPA by HPLC-ECD after deproteinization of plasma is also described and compared with the conversion method. Good agreement was found when plasma DOPA levels exceeded 0.25 mumol/l (y(conversion method) = 0.943x (direct method) + 0.118; n = 60; r = 0.985). The direct method, because of greater simplicity and the possibility of simultaneous measurement of the DOPA metabolite 3-O-methyldopa, is the method of choice with plasma samples from DOPA-treated patients. In non-DOPA treated individuals the conversion method is superior and has proved to be an accurate and sensitive method for the determination of DOPA levels in plasma and cerebrospinal fluid.
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PMID:Determination of 3,4-dihydroxyphenylalanine (DOPA) in plasma and cerebrospinal fluid by high performance liquid chromatography with electrochemical detection. 314 24

Activation of specific receptors for dopamine in the renal vasculature and tubules leads to increases in glomerular filtration, and to diuresis and natriuresis. There is evidence for intrarenal production and release of dopamine, which may originate from two sources: tubular decarboxylation of plasma l-DOPA and a population of dopaminergic sympathetic neurons that innervate the renal cortex. Studies of plasma and urinary catecholamine levels indicate that dopamine is released within the kidney in response to sodium loading and to activation of sensory pathways related to nociception and chemoreception. There is also evidence for deficient renal release of dopamine in patients with renovascular or essential hypertension. Collectively, the available data suggest that intrarenal dopamine has a physiological function in control of blood volume and blood pressure, and that defects in this control may be implicated in the aetiology of some hypertensive states.
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PMID:Endogenous renal dopamine and control of blood pressure. 330 31

Aromatic-L-aminoacid (dopa) decarboxylase (ALAAD) was determined in human plasma by its ability to form dopamine from the substrate 3,4-dihydroxyphenylalanine in the presence of pyridoxal-5-phosphate as cofactor. Dopamine formed was quantitated by high performance liquid chromatography with electrochemical detection. A preincubation step of plasma with the cofactor and dithioerythritol was necessary to obtain optimal reaction conditions. The assay method showed good linearity and reproducibility. The inhibition pattern of the therapeutically used peripheral dopa decarboxylase inhibitors, carbidopa and benserazide, was studied and appeared to be dependent on whether the inhibitor was added before or after the preincubation step. Mean levels in 40 control subjects, in 40 patients with essential hypertension and in 15 patients with phaeochromocytoma, were 34.6 (SD 12.1), 28.5 (SD 10.9) and 34.7 (SD 18.4) mU/l respectively. In the patients with essential hypertension the enzyme level decreased with age (p less than 0.05). Very high levels were found in plasma of two patients with metastatic phaeochromocytoma and in two patients with untreated neuroblastoma, but not in two patients with neuroblastoma after chemotherapy. The method described can be used for measuring uninhibited ALAAD activity in patients treated with benserazide, as well as for measuring total, i.e. the sum of inhibited and uninhibited, ALAAD activity in patients treated with carbidopa.
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PMID:Determination of aromatic-L-amino acid decarboxylase in human plasma. 376 7

Intravenous administration of tritium-labeled 3,4-dihydroxyphenylalanine (dopa) to human subjects resulted in the labeling of endogenous catecholamines and vanillylmandelic acid (VMA). Determination of the changes in specific activity of these compounds with time in fractional collections of urine and in cardiac biopsies from patients undergoing corrective cardiac surgery permitted estimation of apparent turnover rates. The average half-time of the exponential decline in specific activity of labeled urinary norepinephrine was about 8 hr and that of VMA was 11-16 hr in five normal subjects. No significant differences from normal were observed in eight patients with essential hypertension. The average half-life of norepinephrine was only 5 hr in cardiac patients undergoing surgery, and the levels and rate of decline of cardiac norepinephrine specific activity correlated well with the exponential phase of the urinary disappearance curve. There were significant effects of treatment with alpha-methyltyrosine, reserpine, and pargyline hydrochloride on the labeling and apparent turnover rates of norepinephrine and VMA; the effects noted were consistent with known actions of these three drugs. It is suggested that the technique used is a suitable means of assessing "over-all" catecholamine metabolism in man, particulary if combined with quantitative assay of urinary catecholamine metabolites.
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PMID:Catecholamine turnover in normotensive and hypertensive man: effects of antiadrenergic drugs. 567 29

We applied transmitter washout methodology, sampling internal jugular venous plasma via a percutaneously placed catheter, to study CNS norepinephrine release in humans and its relation to peripheral sympathetic activity. Norepinephrine overflows into the venous drainage of the brain, as do its precursor, DOPA, and metabolites DHPG and MHPG, indicating that the blood-brain barrier provides an incomplete impediment to their outward flux from the brain. Pharmacological testing with two drugs which altered CNS norepinephrine turnover, the tricyclic antidepressant desipramine and the ganglionic blocker, trimethaphan, demonstrated a direct relation existed between CNS norepinephrine release and sympathetic nerve firing rates. In essential hypertension, the sympathetic activation commonly present was associated with, and possibly caused by increased CNS release of norepinephrine, manifested in elevated overflow of norepinephrine, MHPG and DHPG from the brain. Bilateral jugular sampling, coupled with a cerebral venous sinus scan to delineate the drainage pattern, demonstrated that this increased norepinephrine release was confined to subcortical forebrain regions.
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PMID:Central nervous system noradrenergic control of sympathetic outflow in normotensive and hypertensive humans. 773 86


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