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

Hypertension is an important risk factor for atherosclerosis and often occurs in association with diabetes mellitus. Specific activities of hydrolases in homogenates of aortas from rats with renal-clip hypertension, normotension following a period of hypertension, and hypertension combined with streptozotocin-induced diabetes mellitus were measured. Enzymes included: neutral alpha-glucosidase, and lysosomal N-acetyl-beta-glucosaminidase, beta-galactosidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 6 or 12 weeks of hypertension, specific activities of all enzymes measured were significantly increased, levels ranging from 24% above normal for cathepsin C to 351% above normal for N-acetyl-beta-glucosaminidase. Six weeks of normotension following 6 weeks of hypertension resulted in restoration to normal of four of the six enzyme activities; the remaining two enzymes were significantly below normal levels. Combined hypertension and diabetes mellitus showed smooth muscle cell levels of four of the five hydrolases measured to be significantly lower than those present with hypertension alone. In every instance, histochemical studies of aortas showed acid phosphatase and N-acetyl-beta-glucosaminidase activities which corresponded to the biochemical findings. These findings indicate profound and discrete effects of two clinical risk factors on vascular smooth muscle cell lysosomes.
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PMID:Hydrolase activities in the rat aorta. II. Effects of hypertension alone and in combination with diabetes mellitus. 65 43

Replication-deficient recombinant adenovirus vectors have been used to transfer foreign genes effectively to a wide variety of cell types in vivo and in vitro. We have now used adenovirus containing either the Escherichia coli beta-galactosidase (beta-gal) gene (AdHCMVsp1LacZ) or the firefly luciferase gene (Ad5-luc3) to test the hypothesis that efficiencies of adenovirus-mediated gene delivery into organ cultures of smooth muscle differ according to the anatomic origin of the muscle. Thoracic aorta and renal artery were isolated from 9-week-old male Sprague-Dawley rats and exposed to adenovirus after 16 hours of incubation with serum-free medium (Dulbecco's modified Eagle's medium). With the use of histochemical methods, beta-gal staining was noted in both endothelial and adventitial cells but not in the muscular media of thoracic aorta and renal artery exposed to AdHCMVsp1LacZ. The efficiency of the transfection, assessed either by counting of beta-gal-stained cells in intact vessels or by measurement of beta-gal activity in tissue extracts, was higher in renal artery than thoracic aorta (P < .05). Consistent with this result, luciferase activity in renal artery exposed to Ad5-luc3 (15.9 +/- 2.1 x 10(6) relative light units per milligram protein) was higher than that in thoracic aorta (8.3 +/- 2.0 x 10(6), P < .05). To determine whether increased efficiency of adenovirus-mediated gene transfer into renal artery is a function of the replication status of vessels, we assessed [3H]thymidine incorporation. [3H]Thymidine uptake by thoracic aorta was only 63% of that in renal artery (P < .05), indicating that more proliferating cells are present in renal artery. We conclude that the efficiency of adenovirus-mediated gene transfer into cultured renal artery is enhanced compared with that into thoracic aorta and propose that the increase in efficiency is related to the higher proliferative activity of renal artery.
Hypertension 1995 Dec
PMID:Heterogeneity of adenovirus-mediated gene transfer in cultured thoracic aorta and renal artery of rats. 749 65

A patient with early infantile galactosialidosis presenting as congenital adrenal hyperplasia with clitoral hypertrophy and arterial hypertension is reported. Serum 17-alpha-OH-progesterone and plasma renin levels were elevated. Adrenal hyperplasia and thickening of the cardiac septum were detected by sonography; however, progressive hepatosplenomegaly, increasingly coarse features, and vacuolization of bone marrow and liver cells suggested a storage disorder. Combined deficiency of beta-galactosidase and sialidase enzyme activity in both lymphocytes and cultured fibroblasts was detected. This patient with early infantile galactosialidosis is the first reported who presented with congenital adrenal hyperplasia.
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PMID:Infantile galactosialidosis presenting with congenital adrenal hyperplasia and renal hypertension. 821 48

Electrophoretic analyses of the urinary proteins of pre-eclamptic patients revealed a decrease in the staining intensity of the protein band representing the Tamm-Horsfall glycoprotein (THP). In the present study the quantitative analysis of the THP excretion rate and the urinary activity of THP oligosaccharide metabolizing glycosidases were investigated. The median THP excretion rate of non-pregnant women (n = 24) was 20 mg/g creatinine (crea.). An increase in the THP excretion rate was seen in pregnancy to a level between 43 mg/g crea. (II. trimester) and 32 mg/g crea. (III. trimester) (n = 29). Hypertension in pregnancy was associated with a decrease in the THP excretion rate to 9 mg/g crea. (n = 85). Post partum, a transient elevated THP excretion rate up to 109 mg/g crea was recorded in the group of hypertensive patients. The urinary activities of the lysosomal beta-mannosidase, alpha-fucosidase, alpha-mannosidase (pH 4.5) and beta-galactosidase increased in normal pregnancy. This effect was most pronounced in the beta-galactosidase activity which increased from 50 U/mg crea. before pregnancy to 280 U/mg crea. at term. Hypertension in pregnancy was associated with a further increase in the activities of the lysosomal glycosidases. In the case of the beta-galactosidase a significant rise from 68 to 310 U/mg crea. was found. The urinary activity of the alpha-mannosidase (pH 5.5) originating from the Golgi apparatus was only elevated in patients with severe pre-eclampsia. Casuistic post partum recordings demonstrated that an elevation of the lysosomal glycosidases activities was followed by a transient increase in the THP excretion rate.
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PMID:The relationship between urinary Tamm-Horsfall glycoprotein excretion and urinary activity of glycosidases in normal pregnancy and pre-eclampsia. 844 58

The tissue kallikrein-kinin system has been postulated to play a role in blood pressure homeostasis and the pathogenesis of clinical hypertension. To demonstrate the potential therapeutic effects of somatic gene delivery in treating hypertension, we used spontaneously hypertensive rats (SHR) as a model. The gene encoding the human tissue kallikrein was used because of its powerful hypotensive action. The human kallikrein DNA constructs were placed under the control of the metallothionein metal response element, the cytomegalovirus promoter/enhancer or the Rous sarcoma virus 3'-LTR. The human tissue kallikrein DNA constructs were incorporated into adenoviral vectors via homologous recombination. The naked plasmid DNA constructs or adenovirus containing the kallikrein gene were first introduced into kidney 293 cells and the expression of human tissue kallikrein was identified by ELISA. The kallikrein gene was delivered into SHR via intramuscular, intravenous, portal vein, intraperitoneal, and intracerebroventricular routes. A single injection of naked human kallikrein DNA constructs caused a prolonged reduction of high blood pressure for up to 8 weeks. Adenoviral-mediated gene delivery results in high efficiency of human tissue kallikrein expression. Immunoreactive human kallikrein was detected in rat serum at the highest level at 1 day post gene delivery. Portal vein delivery of a reporter gene, AdCMV-LacZ, results in intense staining of beta-galactosidase in rat liver, suggesting that recombinant kallikrein is mainly produced in liver and secreted into the circulation. These results show that kallikrein gene delivery causes a sustained reduction of blood pressure in genetically hypertensive rats and provide important information for a potential gene therapy approach to human hypertension and related diseases.
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PMID:Kallikrein gene therapy: a new strategy for hypertensive diseases. 922 51

We tested the effects of overexpression of the endothelial nitric oxide synthase (eNOS) gene in the normal arterial wall by adenoviral-mediated gene transfer. Rabbit carotid arteries were surgically isolated and exposed to adenoviral vectors encoding eNOS (AdeNOS) or beta-galactosidase (Ad betaGal) on the contralateral side. Vector solutions at a concentration of 1 x 10(10) plaque forming units/mL were instilled for 20 minutes before restoration of flow. Arteries were harvested 4 days later for immunostaining, measurement of cGMP, and vasomotor studies. Endothelium-specific gene transfer was confirmed by staining for beta-galactosidase in the Ad betaGal arteries. Immunostaining of en face endothelial cell imprints from AdeNOS-transduced arteries with a monoclonal antibody to eNOS showed increased immunoreactivity. Basal cGMP levels were significantly greater in the AdeNOS-transduced arteries (18.4+/-4.6 versus 4.2+/-0.5 pmol/mg protein; P<.05). Contractions to phenylephrine were significantly reduced in the AdeNOS-transduced arteries (area under curve, 106+/-5 versus 119+/-7; P<.05), but in the presence of the eNOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA, 3 x 10(-4) mol/L), there was no difference between the two (area under curve, 148+/-5 versus 153+/-6; P=NS). Relaxations to acetylcholine obtained during submaximal contractions to phenylephrine were significantly enhanced in the AdeNOS-transduced arteries (EC50, 7.45+/-0.05 versus 7.23+/-0.03; P<.05). We conclude that overexpression of eNOS in the endothelium results in diminished contractile responses, as well as enhanced endothelium-dependent relaxations. These findings imply a possible role for vascular eNOS gene transfer in the treatment of vasospasm and endothelial dysfunction.
Hypertension 1997 Sep
PMID:Enhanced endothelium-dependent relaxations after gene transfer of recombinant endothelial nitric oxide synthase to rabbit carotid arteries. 931 10

Baroreceptor nerve endings are located in the adventitia of the carotid sinuses and aortic arch. The goal of the present study was to develop a method for gene transfer to the carotid sinus adventitia. Replication-deficient adenovirus containing the gene for Escherichia coli beta-galactosidase (beta-Gal) was applied topically to the carotid sinuses of anesthetized rabbits. Transgene expression was localized by histochemical staining and quantified by chemiluminescence assay (Galacto-Light). Possible effects of adenovirus on baroreceptor sensitivity were investigated by recording baroreceptor activity from the vascularly isolated carotid sinus over a pressure range of 0 to 160 mm Hg. Beta-Gal expression in carotid sinus was evident 1 day after virus application, was dose dependent, and was markedly enhanced after 4 days. Expression was restricted to the adventitia of the vessel wall and was not present in vehicle-treated carotid sinuses. Baroreceptor sensitivity measured from carotid sinuses exposed to adenovirus 4 to 5 days beforehand was not altered compared with that measured from control carotid sinuses. In summary, topical application of adenoviral vectors to the carotid sinus provides transgene expression restricted to the region of baroreceptor innervation. The technique provides a novel approach to delineate mechanisms involved in baroreceptor activation and to deliver neuroactive gene products to the baroreceptors.
Hypertension 1997 Sep
PMID:Gene transfer to carotid sinus in vivo: a novel approach to investigation of baroreceptors. 932 10

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme that is crucial to the metabolism of carcinogenic catechols and catecholamines. Regulation of human COMT gene expression may be important in the pathophysiology of various human disorders including estrogen-induced cancers, Parkinson's disease, depression, and hypertension. The gender difference in human COMT activity and variations in rat COMT activity during the estrous cycle led us to explore whether estrogen can regulate human COMT gene transcription. Our Northern analyses showed that physiological concentrations of 17-beta-estradiol (10(-9)-10(-7) M) could decrease human 1. 3-kilobase COMT mRNA levels in MCF-7 cells in a time- and dose-dependent manner through an estrogen receptor-dependent mechanism. Two DNA fragments immediately 5' to the published human COMT gene proximal and distal promoters were cloned. Sequence analyses revealed several half-palindromic estrogen response elements and CCAAT/enhancer binding protein sites. By cotransfecting COMT promoter-chloramphenicol acetyltransferase reporter genes with human estrogen receptor cDNA and pSV-beta-galactosidase plasmids into COS-7 cells, we showed that 17-beta-estradiol could down-regulate chloramphenicol acetyltransferase activities, and COMT promoter activities dose-dependently. Functional deletion analyses of COMT promoters also showed that this estrogenic effect was mediated by a 280 base pair fragment with two putative half-palindromic estrogen response elements in the proximal promoter and a 323-base pair fragment with two putative CCAAT/enhancer binding protein sites in the distal promoter. Our findings provide the first evidence and molecular mechanism for estrogen to inhibit COMT gene transcription, which may shed new insight into the role of estrogen in the pathophysiology of different human disorders.
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PMID:Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription. 1038 81

Vasopressin is synthesized by magnocellular neurons in supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei and released by their axon terminals in the neurohypophysis (NH). With its actions as an antidiuretic hormone and vasoactive agent, vasopressin plays a pivotal role in the control of body fluids and cardiovascular homeostasis. Because of its well-defined neurobiology and functional importance, the SON/PVN-NH system is ideal to establish methods for gene transfer of genetic material into specific pathways in the mouse central nervous system. In these studies, we compared the efficiency of transferring the gene lacZ, encoding for beta-galactosidase (beta-gal), versus a gene encoding for green fluorescent protein by using replication-deficient adenovirus (Ad) vectors in adult mice. Transfection with viral concentrations up to 2 x 10(7) plaque-forming units per coverslip of NH, PVN, and SON in dissociated, cultured cells caused efficient transfection without cytotoxicity. However, over an extended period of time, higher levels (50% to 75% of the cells) of beta-gal expression were detected in comparison with green fluorescent protein (5% to 50% of the cells). With the use of a stereotaxic approach, the pituitary glands of mice were injected with Ad (4 x 10(6) plaque-forming units). In material from these animals, we were able to visualize the expression of the beta-gal gene in the NH and in magnocellular neurons of both the PVN and SON. The results of these experiments indicate that Ad-Rous sarcoma virus promoter-beta-gal is taken up by nerve terminals at the injection site (NH) and retrogradely transported to the soma of the neurons projecting to the NH. We conclude that the application of these experimental approaches will provide powerful tools for physiological studies and potential approaches to deliver therapeutic genes to treat diseases.
Hypertension 1999 Oct
PMID:Adenovirus-mediated gene delivery to hypothalamic magnocellular neurons in mice. 1052 56

Adrenal zona glomerulosa (ZG) cells do not contain nitric oxide (NO) synthase (NOS). We conferred endothelial NOS activity onto adrenal ZG cells through transduction with a recombinant adenovirus encoding the endothelial NOS gene (AdeNOS) to determine the effect of endogenous NO on aldosterone synthesis. A 135-kDa protein band immunoreactive to anti-endothelial NOS antibody was observed in Western blots of AdeNOS-transduced ZG cells but not in control cells or cells transduced with adenovirus encoding the beta-galactosidase gene (AdbetaGal). Nitrate/nitrite production in AdeNOS-transduced ZG cells increased from 0.15+/-0.01 to 0.27+/-0.01 micromol/L after stimulation with 1 nmol/L angiotensin II. The treatment of AdeNOS-transduced cells with 30 micromol/L L-nitro-arginine decreased angiotensin II-stimulated nitrite production from 0.27+/-0. 01 to 0.17+/-0.01 micromol/L. Basal and angiotensin II-stimulated nitrite production was not increased in AdbetaGal-transduced or control cells. AdeNOS-transduced cells demonstrated diaminofluorescein-2 diacetate fluorescence, which was blocked by pretreatment with L-nitro-arginine. Angiotensin II-stimulated aldosterone synthesis decreased from 5123+/-177 pg/mL in AdbetaGal-transduced ZG cells to 72+/-27 pg/mL in AdeNOS-transduced cells. Treatment with the NOS inhibitor thiocitrulline (30 micromol/L) increased angiotensin II-stimulated aldosterone synthesis to 2158+/-45 pg/mL after AdeNOS transduction. These data demonstrate that adenovirus-mediated gene transfer of eNOS in ZG cells results in the expression of active endothelial NOS enzyme and that this endogenous NO production by ZG cells decreases aldosterone synthesis.
Hypertension 2000 Jan
PMID:Inhibition of adrenal cell aldosterone synthesis by endogenous nitric oxide release. 1064 19


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