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)

Serum dopamine beta-hydroxylase (DBH) activity was comparable in eight adrenalectomized patients and in 41 normal volunteers (37.8 +/- 3.6 vs. 40.0 +/- 4.0 IU), but were very low in four patients with severe diabetic autonomic neuropathy (6.7 +/- 4.2). These observations suggest that the major source of DBH activity in human serum is probably the sympathetic nervous system. Serum DBH activity was also significantly lower in seven patients with low renin essential hypertension than in 17 patients with normal renin hypertension (19.9 +/- 4.3 vs. 43.9 +/- 5.0 IU, P less than 0.05). Dietary sodium depletion, a stimulus for catecholamine secretion, produced only a small increase in serum DBH activity in supine normal volunteers (26.5 +/- 10.4 to 33.9 +/- 11.4, P less than 0.05; n = 7) and in five adrenalectomized patients (33.0 +/- 12.7 to 44.1 +/- 15.2, P = 0.06). Plasma renin activity increased more than 3-fold in these same subjects, and did not correlate with serum DBH activity. Similarly, 4 hours of ambulation produced only a small increase in serum DBH activity which did not correlate with plasma renin activity. The small magnitude of these responses to physiological stimuli of the sympathetic nervous system diminishes the potential clinical usefulness of measurement of serum DBH activity. Further studies utilizing direct correlation of plasma and urine catecholamines with serum DBH activity are needed to establish its relationship to sympathetic nervous system activity.
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PMID:Serum dopamine beta-hydroxylase as an index of sympathetic nervous system activity in man. 124 23

Previous investigations have suggested that significant hypotension during hemodialysis may result from abnormalities of sympathetic nervous system activity. To further evaluate these phenomena, plasma dopamine beta-hydroxylase (D beta H) and cold pressor test (proposed indexes of efferent sympathetic nervous system activity) and amyl nitrite inhalation (an index of the entire baroreceptor reflex arc) were studied in two groups of patients: group I, patients exhibiting a mean arterial pressure decrease to less than 70 mm Hg during less than 10% of dialyses; group II (hemodialysis hypotension), patients with a mean arterial pressure decrease to less than 70 mm Hg during more than 90% of dialyses. The groups were similar with respect to plasma renin activity, renin response to ultrafiltration, age, duration of dialysis, nerve conduction velocity, plasma protein concentration, hematocrit, dialysis weight change, resting heart rate, sex, race, blood pressure and heart rate response to cold pressor test, and 125I-albumin plasma volume. Supine mean arterial pressure was higher in patients with hemodialysis hypotension than in patients without hemodialysis hypotension (group I) both before and after dialysis. Plasma D beta H activity was significantly higher in patients with hemodialysis hypotension (group II) than in group I both before and after dialysis. Amyl nitrite inhalation, expressed as change in delta R-R interval/mean arterial pressure decrease, was less in hemodialysis hypotension patients. These results suggest that hemodialysis hypotension may result from a lesion in the baroreceptors, cardiopulmonary receptors, or visceral afferent nerves. Furthermore, elevated mean arterial pressure in patients with hemodialysis hypotension may be neurogenic in origin, as reflected by plasma D beta H activity, and appears similar to the hypertension that follows baroreceptor deafferentation of experimental animals.
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PMID:Adrenergic regulation of blood pressure in chronic renal failure. 126 65

Regulation of catecholamine biosynthesis is crucial in the adaptation to various physiological conditions, such as stress, and in several disorders, including hypertension and depression. In this study we have found that in PC12 cells, the mRNA levels of dopamine beta-hydroxylase (DBH), the enzyme that catalyzes the formation of norepinephrine from dopamine, can be regulated by glucocorticoids and cyclic AMP (cAMP) analogues. Treatment with dexamethasone increased DBH mRNA levels by 6 h. with maximal elevation (four- to fivefold) obtained after 1 day of exposure, and these levels were maintained for up to 4 days. DBH mRNA levels were also elevated on treatment of PC12 cells with 8-bromo cAMP for 8 h to 1 day. The response to 8-bromo cAMP, however, was bimodal, because DBH mRNA levels declined below control values on treatment for > 1 day. In combined treatments with 8-bromo cAMP and dexamethasone, the cAMP effect was dominant. To begin to characterize the regulation of DBH mRNA, genomic clones for rat DBH were isolated, and 1 kb of the 5' flanking region was sequenced. Several putative regulatory elements, which may be involved in cAMP and glucocorticoid regulation, were identified, including two adjacent cAMP response elements, another element that can also bind members of the ATF/CREB family of transcription factors, a NF-kappa B-like sequence, several AP-2 sites, and three core glucocorticoid receptor binding sequences.
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PMID:Regulation of expression of dopamine beta-hydroxylase in PC12 cells by glucocorticoids and cyclic AMP analogues. 135 11

This article presents some aspects of the role of sympathetic efferent nerves in the regulation of blood pressure in humans. Lessons have been learned from disorders that cause either sympathetic underactivity or overactivity. In chronic autonomic failure, pressor stimuli (mental arithmetic, isometric exercise, or cold) are unable to raise blood pressure, whereas stimuli that normally activate sympathetic efferent nerves to maintain blood pressure (head-up tilt, exercise, and food ingestion) can cause marked hypotension. Recognition of specific defects, such as the inability to synthesize norepinephrine in isolated dopamine beta-hydroxylase deficiency, suggests that sympathetic nerves may influence blood pressure regulation through nonadrenergic mechanisms (dopamine, neuropeptides, and purines). Tetraplegic patients with high cervical cord transection also have sympathetic impairment and postural hypotension, but this is less of a clinical problem because of compensatory hormonal and other mechanisms. Tetraplegic patients are unique as they also may have severe paroxysmal hypertension because of increased spinal sympathetic reflex activity. The pathophysiological mechanisms responsible for this exaggerated response include changes in postsynaptic adrenergic receptor numbers and their sensitivity, the actions of nonadrenergic cotransmitters, and the lack of sympathoneural pathways from the brain that are severed by the lesion. Finally, the putative role of the sympathetic nervous system in hypertension with unilateral renal artery stenosis, which initially is humorally mediated, is discussed. The centrally acting sympatholytic agent clonidine is effective in lowering blood pressure in renovascular hypertension independently of humoral factors when multiple agents have failed.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Nov
PMID:Role of sympathetic efferent nerves in blood pressure regulation and in hypertension. 193 84

Rats on calcium-deficient diets developed hypocalcemia, hyperparathyroidism and hypertension and showed an increase in plasma catecholamines. Adrenal gland catecholamines were decreased while tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) were found to be increased, as compared to controls. In contrast, no significant differences were found between controls and parathyroidectomized rats in plasma catecholamines, and catecholamines, TH and DBH of the adrenal gland. These findings seem to indicate that the genesis of hypertension in rats on a low calcium diet is secondary to hyperparathyroidism caused by a low calcium diet. Furthermore, some relation between catecholamines and parathyroid hormone seems to exist in the regulation of blood pressure in rats.
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PMID:Dietary calcium deprivation increased the levels of plasma catecholamines and catecholamine-synthesizing enzymes of adrenal glands in rats. 196 34

In the face known antihypertensive action of small dopamine (DA) concentrations, serum free and conjugated dopamine levels were determined during orthostatic impulse. It was also estimated, whether correlation between blood pressure changes and serum dopamine concentration existed under those conditions. 9 patients with borderline hypertension, 8 with fixed hypertension and 5 healthy volunteers (control group) underwent the 10 minute passive tilt up test. It caused significant decrease of free DA concentration in healthy men as well as in those with borderline hypertension and conjugated DA level in both groups of patients with primary hypertension. Blood pressure increased only in patients with borderline hypertension. Most expressed changes in dopamine concentration were also observed in those patients and they only had increased serum DBH activity. Blood pressure changes inversely correlated with changes of serum free and/or conjugated DA levels in the control group and in patients with primary hypertension. Authors stated basing on this study results, that serum DA level lowering caused by the orthostatic impulse can be one of phenomenons enable adaptation for a vertical position.
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PMID:[Is there a correlation between serum dopamine level and blood pressure during upright posture?]. 227 80

Patients with autonomic failure secondary to dopamine beta-hydroxylase deficiency lack the enzyme activity necessary for the conversion of dopamine to norepinephrine in sympathetic nerve terminals and the adrenal medulla. These patients have virtually undetectable norepinephrine and epinephrine in plasma and cerebrospinal fluid. The presence of intact sympathetic nerve activity in these patients has been suggested by the enhanced release of dopamine (but not norepinephrine) in response to maneuvers that augment sympathetic outflow in normal subjects. In the present study, we recorded sympathetic nerve traffic by using microneurography in a patient with dopamine beta-hydroxylase deficiency and measured sympathetic neural responses to static exercise, the cold pressor test, and pharmacological alterations of blood pressure. At rest, sympathetic nerve activity was abundant and was modulated in a normal manner by handgrip (+278%), the cold pressor test (+169%), hypotension induced with isoproterenol (+102%), and hypertension induced with phenylephrine (-85%). These results provide the first electrophysiological evidence for intact regulation of sympathetic neural outflow in a patient with dopamine beta-hydroxylase deficiency and suggest that central norepinephrine and epinephrine pathways believed essential for the control of sympathetic neurotransmission in humans may be supplanted by alternative redundant mechanisms.
Hypertension 1990 Jan
PMID:Reflex control of sympathetic nerve activity in dopamine beta-hydroxylase deficiency. 229 11

Previous studies from our laboratories demonstrated that dietary NaCl supplementation in NaCl-sensitive spontaneously hypertensive rats elevates blood pressure, increases peripheral sympathetic nervous system activity, and depresses endogenous norepinephrine stores and turnover in the anterior hypothalamus. These findings suggest that reduced noradrenergic input to sympathoinhibitory neurons in anterior hypothalamus contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats. The current study tested the hypothesis that dietary NaCl supplementation depresses endogenous norepinephrine stores and turnover in anterior hypothalamus of two other NaCl-sensitive models of hypertension, the Dahl salt-sensitive rat and the deoxycorticosterone acetate/NaCl hypertensive rat, thus increasing blood pressure by reducing noradrenergic input to the anterior hypothalamus. Dahl salt-sensitive rats were fed a high (8%) NaCl diet, and deoxycorticosterone acetate/NaCl rats rats drank 1% NaCl solution ad libitum for 2 or 4 weeks. Age-matched Dahl salt-sensitive rats fed a basal 1% NaCl diet and uninephrectomized Sprague-Dawley rats drinking tap water were controls. Regional brain catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Norepinephrine turnover in hypothalamus (anterior, posterior, and ventral regions) and brain stem (pons and medulla) was assessed using the dopamine beta-hydroxylase inhibitor 1-cyclohexyl-2-mercapto-imidazole. High NaCl treatment caused significant elevations in blood pressure in Dahl salt-sensitive and deoxycorticosterone acetate/NaCl rats, but endogenous norepinephrine levels and turnover rates were not significantly different in anterior hypothalamus or any other brain region studied between the NaCl-supplemented and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Jul
PMID:NaCl does not affect hypothalamic noradrenergic input in deoxycorticosterone acetate/NaCl and Dahl salt-sensitive rats. 236 46

Twenty-three patients [mean age 49.7 +/- 5.6 years (WHO II-III)] with severe hypertension and not responding to previous drug treatment were included in the study to evaluate the effect of nitrendipine (NTP) as monotherapy and also in combination with propranolol (PRO). After a control period of 10 days, NTP was started with 20 mg twice a day and titrated to the maximal dosage of 2 X 40 mg/day. After 1 week of NTP treatment, PRO was added in increasing dosage to a maximal 2 X 100 mg/day. NTP lowered systolic and diastolic blood pressure (BP) significantly (supine BP from 182/119 +/- 19/9 to 157/98 +/- 16/9 mm Hg). After combination with PRO, systolic BP was decreased additionally (supine BP from 157/98 +/- 16/9 to 150/97 +/- 19/9 mm Hg). Plasma norepinephrine (NE) was increased by NTP (from 1.82 +/- 0.78 to 2.38 +/- 1.08 nmol/l, p less than 0.01) and remained elevated during PRO treatment (2.76 +/- 1.10 nmol/l). Plasma renin activity (PRA) showed no significant changes by NTP. Additional effect of PRO on BP correlated significantly with NE and PRA after the NTP period. Plasma epinephrine and dopamine beta-hydroxylase remained unchanged. NTP decreased systemic resistance, calculated from isotope dilution technique (p less than 0.05); after combination with PRO no additional significant changes were registered. Nitrendipine is an effective alternative in so-called therapy-resistant hypertension.
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PMID:Nitrendipine treatment in so-called therapy-resistant arterial hypertension; effect as monotherapy and in combination with propranolol on blood pressure, heart rate, other hemodynamic parameters, plasma renin activity, and catecholamines. 246 60

Secretory components of the adrenal medulla were compared in normotensive Wistar-Kyoto (WKY) rats and in stroke-prone spontaneously hypertensive rats (SHRSP) at both 4 and 12 months of age. Noradrenaline, adrenaline, dopamine, neuropeptide Y, and chromogranins A and B were significantly higher in adrenal glands of SHRSP than those of WKY rats at 4 months. At 12 months, the levels of these components in SHRSP had increased even more (about 200% in WKY rats). There was no change in the relative composition of the adrenal "secretory cocktail." Neither the chromogranin A/chromogranin B ratio nor their apparent proteolytic processing in chromaffin granules differed between SHRSP or WKY rats. The lack of a significant change in membrane-bound cytochrome b561 and the small increase in dopamine beta-hydroxylase suggest that the higher levels of secretory components in SHRSP are not simply caused by an increase in the number of chromaffin granules, but possibly by a selective increase in the secretory content of these organelles providing a larger package for quantal release by exocytosis. This may be relevant for the elevation of blood pressure in this strain. The immunological methods described in this paper allow for the first time a determination of the secretory quantal levels in catecholamine storage. This should be useful for further studies in hypertensive models.
Hypertension 1989 May
PMID:An increased pool of secretory hormones and peptides in adrenal medulla of stroke-prone spontaneously hypertensive rats. 256 78


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