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)

Tyrosine hydroxylase is considered to be the rate-limiting enzyme in the synthesis of catecholamines in both the central and peripheral nervous system. Increased or decreased neuronal activity, stress, lesions, drug effects, endocrinological manipulations and experimental models of hypertension are associated with alterations in tyrosine hydroxylase activity in the central nervous system. In many of these instances, the changes in the activity of tyrosine hydroxylase in the central nervous system that occur are localized to discrete catecholaminergic pathways and nuclei in the brain. The purpose of this review is to summarize and assess this information and to provide insight into the function of catecholamine systems in the brain and their interactions with other putative neurotransmitter systems.
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PMID:Tyrosine hydroxylase regulation in the central nervous system. 613 60

We have postulated that the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) are coded for by similar genes. To analyze the structural relationship of genes coding for these enzymes, we have cloned DNAs complementary (cDNA) to DBH and PNMT messenger RNAs (mRNAs). Using hybrid selection analysis to identify the cDNA clones positively, we discovered cross-hybridization between DBH cDNA clones and PNMT mRNA and between PNMT cDNA clones and DBH mRNA. Further analysis by RNA blot hybridization revealed that the DBH cDNA probe hybridized predominantly to a 5500 nucleotide mRNA and less strongly to a 1100 nucleotide species, and the PNMT cDNA probe hybridized strongly to the 1100 nucleotide mRNA and weakly to the 5500 nucleotide message. DNA blot hybridization analysis demonstrated that DBH and PNMT cDNA probes hybridized to several common restriction fragments of total cellular DNA. The evidence presented here suggests the existence of homologous gene-coding regions in DBH and PNMT cDNAs. These homologies may be the result of duplication of a common ancestral gene. DNA blot analysis suggests that these enzymes are coded for by single genes, which may be located in close proximity to each other in the DNA, and points to the existence of either a single gene or linked genes coding for all catecholamine enzymes.
Hypertension
PMID:Molecular biology of catecholamine neurons. Similar gene hypothesis. 614 99

To further define central and peripheral sympathetic nerve activity in the one-kidney and two-kidney, one-clip models of renovascular hypertension, plasma catecholamines and regional brain norepinephrine of these models were compared with the activities of their brain biosynthetic enzymes: tyrosine hydroxylase (TYH) and dopamine-beta-hydroxylase (DBH). Findings in the groups of 20 one-kidney and 17 two-kidney female Wistar rats were compared with those in 10 sham-operated rats. Systolic blood pressure, measured indirectly, and the mean arterial pressure, measured directly from the femoral arteries, verified development of renovascular hypertension in both the one and two-kidney animals. Plasma norepinephrine increased from 248 +/- 46 to 401 +/- 66 pg/ml in the one-kidney group only (p < 0.001). Hypothalamic TYH and DBH activities of the one-kidney animals were 48 and 34% greater than those of the two-kidney animals and 28 and 39% greater than the sham-operated animals. The multiple t-test indicated significant differences between the mean hypothalamic THY of the one- and two-kidney groups and between the hypothalamic DBH of the one-kidney animals and those of the two-kidney and sham groups (alpha = 0.05). Moreover, the mean norepinephrine content of the hypothalamus in the one-kidney animals was 66% greater than that of the two-kidney and sham groups (p < 0.05). These findings suggest that central noradrenergic pathways of the hypothalamus may be involved in the genesis of one-kidney renovascular hypertension.
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PMID:Increased hypothalamic noradrenergic activity in one-kidney, one-clip renovascular hypertensive rats. 616 Mar 32

Lesions in the tissue at the anteroventral end of the third ventricle (AV3V area) prevent the development of a variety of forms of experimental hypertension. This region receives afferents from several cell groups which have been implicated in cardiovascular regulation, including the nucleus of the solitary tract and neurons in the ventrolateral medulla. About 70% of the nucleus of the solitary tract neurons which could be retrogradely labeled from the AV3V area stained immunohistochemically for tyrosine hydroxylase, but not phenylethanolamine-N-methyltransferase, and were therefore presumably noradrenergic. About half of the neurons in the rostral part of the ventrolateral medulla which innervated the AV3V area stained for both enzymes, and thus were apparently adrenergic. These medullary catecholaminergic inputs to the AV3V area may be of importance in explaining recent data concerning the roles of both regions in experimental hypertension.
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PMID:Medullary catecholamine inputs to the anteroventral third ventricular cardiovascular regulatory region in the rat. 632 72

The synthetic catechol, U-0521, (3',4'-dihydroxy-2-methylpropiophenone) is a competitive inhibitor of both tyrosine hydroxylase and catechol-O-methyltransferase. Continuous subcutaneous administration of 10 mumoles per day of U-0521 via Alzet osmotic minipumps to adult male Spontaneously Hypertensive Rats (SHR) reduced blood pressure from 160 mmHg to 125 mmHg. This effect occurred within two days, persisted for the two weeks that the pumps were in place, and reversed gradually upon cessation of U-0521 administration. Similar treatment of U-0521 to normotensive Wistar Kyoto rats (WKY) did not result in a similar hypotentensive effect. Subcutaneous administration of the same dose to juvenile SHRs led to a blockade in the expression of hypertension. After the five week treatment period, the blood pressure of the U-0521 treated animals escalated rapidly to match the saline treated controls. The antihypertensive effect of U-0521 on SHRs also occurred when the compound was delivered by the oral route at the rate of 50 mg/kg/day.
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PMID:The antihypertensive effect of U-0521 (3',4'-dihydroxy-2-methylpropiophenone). 717 11

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter in the central nervous system [Y. Misu et al. (1995) Adv. Pharmac. 32, 427-459]. L-DOPA as a probable neurotransmitter for the primary baroreceptor afferents tonically functions to mediate cardiodepressor control in the nucleus tractus solitarii and also tonically functions to mediate cardiopressor control in the rostral ventrolateral medulla of rats. We further attempted to clarify whether a transmitter-like L-DOPA system is altered in these areas of adult spontaneously hypertensive rats. By microdialysis in the left nucleus tractus solitarii area, the basal L-DOPA release was lower in spontaneously hypertensive rats than that in Wistar-Kyoto rats. This release was partially reduced by tetrodotoxin (1 microM) to the same absolute levels in the two strains. Tonic neuronal L-DOPA release is impaired in this nucleus of spontaneously hypertensive rats. This impairment is not secondarily due to decrease in formation or increase in decarboxylation of L-DOPA, since tyrosine hydroxylase activity was increased in spontaneously hypertensive rats, compared to Wistar-Kyoto rats, while no difference of L-aromatic amino acid decarboxylase activity was seen in the caudal dorsomedial medulla including the nucleus. L-DOPA (10-300 ng) microinjected into the nucleus produced dose-dependent hypotension and bradycardia. A maximum depressor response of spontaneously hypertensive rats to L-DOPA at higher doses was slightly greater than that of Wistar-Kyoto rats. On the other hand, in the left rostral ventrolateral medulla, the basal L-DOPA release was higher in spontaneously hypertensive rats than that in Wistar-Kyoto rats. This release was also partially reduced by tetrodotoxin to the same absolute levels in the two strains. Tonic neuronal L-DOPA release is enhanced in spontaneously hypertensive rats. This enhancement seems to include partially a decrease in decarboxylation of L-DOPA, since L-aromatic amino acid decarboxylase activity was decreased in spontaneously hypertensive rats compared to Wistar-Kyoto rats, while no difference in tyrosine hydroxylase activity was seen. L-DOPA (10-600 ng) produced dose-dependent hypertension and tachycardia. Importantly, a pressor response of spontaneously hypertensive rats to L-DOPA at lower doses was slightly greater than that of Wistar-Kyoto rats. L-DOPA seems to play a transmitter-like role in blood pressure regulation at levels of the nucleus tractus solitarii and rostral ventrolateral medulla in rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Altered tonic L-3,4-dihydroxyphenylalanine systems in the nucleus tractus solitarii and the rostral ventrolateral medulla of spontaneously hypertensive rats. 747 14

We investigated the effects of castration and testosterone propionate on tyrosine hydroxylase mRNA, its activity, and catecholamine synthesis in the adrenal medulla of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Four-week-old male rats were castrated. Testosterone propionate (500 micrograms per rat) was administered subcutaneously twice a week to castrated rats (between 14 and 25 weeks of age). Systolic pressure was measured at the age of 25 weeks, and rats were decapitated. The systolic pressure of castrated SHR was significantly lower than that of control and testosterone-replaced SHR. Epinephrine and norepinephrine levels, tyrosine hydroxylase activity, and tyrosine hydroxylase mRNA in the adrenal medulla of castrated SHR were significantly lower than in control and testosterone-replaced SHR. Systolic pressure and epinephrine and norepinephrine levels, tyrosine hydroxylase activity, and tyrosine hydroxylase mRNA levels in the adrenal medulla of WKY showed no significant differences among the control, castrated, and testosterone-replaced groups. These results suggest that androgens contribute to the development and maintenance of hypertension in SHR via sustained enhancement of tyrosine hydroxylase synthesis in the adrenal medulla, leading to increased epinephrine and norepinephrine levels.
Hypertension 1995 Jul
PMID:Influence of androgen on tyrosine hydroxylase mRNA in adrenal medulla of spontaneously hypertensive rats. 760 26

To investigate the involvement of peripheral catecholamines in the development of Dahl-Iwai salt-sensitive (DIS/Eis) hypertension, we performed immunohistochemical staining of tyrosine hydroxylase (TH) in the superior cervical ganglia (SCG) of DIS/Eis rats and Dahl-Iwai salt-resistant (DIR/Eis) rats, and in situ hybridization histochemistry for demonstration of TH mRNA localization in the SCG of these rats. DIS/Eis and DIR/Eis rats were fed on a high (8%) salt diet or on a low (0.3%) salt diet for 4 weeks. Nerve cells in the SCG of DIS/Eis high salt rats exhibited more intense TH-immunoreactivity (P < 0.01) and hybridization signals (P < 0.01) than those of the other experimental groups. These findings suggest that activation of peripheral sympathetic nerves may account for hypertension in DIS/Eis rats on a high salt diet.
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PMID:Effect of dietary NaCl on tyrosine hydroxylase in the superior cervical ganglia of Dahl rats. 762 44

In three separate experiments, 4 to 5-week-old spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto [WKy]) were exposed to hypobaric hypoxia (simulated altitude = 3658 m) for 3 hr, 3 days, or 3 weeks. Comparable groups were maintained in ambient laboratory conditions (normoxia). Hypoxia prevented the increase in blood pressure noted in 8-week-old normoxic SHR. Right ventricular hypertrophy first occurred after 3 days of hypoxia, and was found in both SHR and WKy. Catecholamine turnover was measured using the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine. In myocardium, both strains evidenced hypoxia-induced changes in norepinephrine (NE) turnover, which was increased at 3 hr, normalized at 3 days, and increased again at 3 weeks. Reduced basal NE concentration at 3 days indicated a temporary deficit in synthetic capacity, which would allow maintenance of a heightened neuronal output. Catecholamine turnover in right and left ventricles differed little in response to hypoxia, in spite of differential hemodynamic demands on SHR versus WKy or on right versus left ventricle. In contrast to findings in myocardium, significant interactive effects between strain and altitude exposure were noted for adrenal catecholamine turnover. Specifically, hypoxia exerted a suppressive influence in SHR that was not evident in WKy, and this may represent an important component of hypoxia-induced protection against the development of spontaneous hypertension.
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PMID:Time-dependent changes in catecholamine turnover in spontaneously hypertensive rats exposed to hypoxia. 770 Aug 91

We investigated the effects of castration and testosterone propionate on sympathetic nervous systems in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Four-week-old male rats were castrated. For replacement of androgen, testosterone propionate (500 micrograms/rat) was administered subcutaneously 2 times a week to castrated rats after their 14th week. The systolic blood pressure of the castrated SHR (44 weeks) was significantly lower than those of intact SHR and testosterone-replaced SHR. The norepinephrine (NE) levels and the tyrosine hydroxylase (TH) activities in the abdominal aorta and mesenteric artery of castrated SHR (45-50 weeks) were significantly lower than those of intact SHR. The NE levels and the TH activities in these blood vessels of testosterone-replaced SHR recovered to the levels obtained in those of intact SHR. As well as the systolic blood pressure, the NE levels and TH activities in blood vessels of WKY were significantly lower than those of intact SHR and showed no significant difference among the three groups. These results suggest that androgen may contribute to the development of hypertension in SHR via sustained enhancement of TH activity in blood vessels leading to increased NE level.
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PMID:Possible involvement of androgen in increased norepinephrine synthesis in blood vessels of spontaneously hypertensive rats. 772 20


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