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

Nitric oxide (NO) is an important intercellular signaling molecule synthesized in diverse human tissues by proteins encoded by a family of NO synthase (NOS) genes. The similarity of sequence and cofactor binding sites has suggested that the NOS genes may also be related to cytochrome P450 reductase, as well as to plant and bacterial oxidoreductases. Endothelial NOS activity is a major determinant of vascular tone and blood pressure, and in several important (and sometimes hereditary) disease states, such as hypertension, diabetes, and atherosclerosis, the endothelial NO signaling system appears to be abnormal. To explore the relationship of the endothelial NOS gene to other similar genes, and to delineate the genetic factors involved in regulating endothelial NOS activity, we isolated the human gene encoding the endothelial NOS. Genomic clones containing the 5' end of this gene were identified in a human genomic library by applying a polymerase chain reaction (PCR)-based approach. Identification of the human gene for endothelial NOS (NOS3) was confirmed by nucleotide sequence analysis of the first coding exon, which was found to be identical to its cognate cDNA. The NOS3 gene spans at least 20 kb and appears to contain multiple introns. The transcription start site and promoter region of the NOS3 gene were identified by primer extension and ribonuclease protection assays. Sequencing of the putative promoter revealed consensus sequences for the shear stress-response element, as well as cytokine-responsive cis regulatory sequences, both possibly important to the roles played by NOS3 in the normal and the diseased cardiovascular system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene. 751 68

Previously, we have reported two major alpha 2-adrenergic receptor transcripts in rat brain of 3.8 and 3.0 kb and the cloning and characterization of the rat brain complementary DNA (cDNA) (RB alpha 2C) specific for the 3.0-kb messenger RNA. In this report, we used rat brain cDNAs specific for the 3.0 and 3.8 kb transcripts, which encode the alpha 2C- and alpha 2A-adrenergic receptors, respectively, and the RNG alpha 2 cDNA, which encodes for the nonglycosylated alpha 2B-adrenergic receptor in rat, to study tissue-specific expression of the three alpha 2-adrenergic receptor genes in rat. To eliminate cross-hybridization of probes with transcripts from other alpha 2 genes, we subcloned fragments that encode for the highly divergent third cytoplasmic loop of each rat alpha 2-adrenergic receptor cDNA and used RNase protection analysis to detect specific transcripts. We show that the three rat alpha 2-adrenergic receptor genes have diverse patterns of tissue expression, and although transcripts specific for each alpha 2-adrenergic receptor gene are found in brain and kidney, the levels of expression of each subtype differ in these tissues. We speculate on the significance of tissue-specific expression of the alpha 2-adrenergic receptor genes.
Hypertension 1993 Jun
PMID:Diverse tissue expression of rat alpha 2-adrenergic receptor genes. 768 25

To clarify the role of PDGF A-chain in hypertensive vascular hypertrophy of spontaneously hypertensive rats (SHRs), we studied levels of PDGF A-chain gene expression and transcription factors related to the gene in vascular smooth muscle cells (VSMCs) of SHRs in vivo. RNase protection assay and in situ hybridization showed that PDGF A-chain mRNA levels in VSMCs of SHRs were twofold higher than in those of normotensive Wistar-Kyoto rats. Gel retardation assays showed that levels of Sp1 and AP-2 in VSMCs of SHRs were twofold more abundant than in those of Wistar-Kyoto rats. Treatment with four pharmacologically different species of antihypertensive drugs for 2 wk decreased the levels of both PDGF A-chain mRNA and Sp1, but not AP-2 level in VSMCs of SHRs with regression of aortic hypertrophy, indicating that increases in levels of both PDGF A-chain mRNA and Sp1 in VSMCs of SHRs were associated with high blood pressure. These results suggest that high blood pressure is a stimulus which upregulates PDGF A-chain gene expression in VSMCs of SHRs, resulting in an autocrine enhancement in hypertensive vascular hypertrophy, and that the activation of the gene may be mediated through increases in Sp1 in these cells.
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PMID:Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy. 788 63

Angiotensin I-converting enzyme (ACE) is known to be present at the surface of endothelial cells and also in the adventitia in large vessels. The presence of ACE in the vascular smooth muscle remains controversial. We microdissected segments of adventitia and media with or without endothelium from a region devoid of collateral arteries. The membrane-bound ACE activity in the media averaged 41% (pmol [glycine-1-14C]hippuryl-L-histidyl-L-leucine hydrolyzed.g tissue-1.min-1) of the values found in the whole aorta, whereas the adventitia contained only 6%. Immunoreactive ACE in media was characterized by Western blotting. ACE mRNAs were detected and characterized after polymerase chain amplification in isolated media. Angiotensin I and angiotensin II were equally able to contract medial rings, and the response to angiotensin I was blocked by enalaprilat. In aortas of two-kidney, one-clip hypertensive rats, there was an increase in ACE mRNA estimated by ribonuclease protection assay (P = 0.02) and in ACE activity at 15 days and 1 and 3 mo after clipping. This corresponded to a 1.5- to 2-fold increase in the ACE activity of both the media and the adventitia compared with sham-operated rats (P < or = 0.02). Thus ACE gene expression occurs in smooth muscle of rat aorta, which contains roughly the same amount of enzyme as the endothelium and readily converts angiotensin I to angiotensin II. ACE in the medial layer and the adventitia is upregulated in renovascular hypertension.
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PMID:ACE in three tunicae of rat aorta: expression in smooth muscle and effect of renovascular hypertension. 797 8

While growth of blood vessels is important in hypertension, relatively little is known about the contribution of catecholamines. Using isolated rat aorta and cultured smooth muscle cells, we examined adrenergic stimulation of gene expression. Phenylephrine, a selective alpha 1 adrenergic receptor agonist, caused a rapid and transient increase in c-fos mRNA accumulation which was inhibited by prazosin, an alpha 1 receptor antagonist. Similarly, phenylephrine stimulated c-jun and c-myc mRNA accumulation. Chloroethyl-clonidine, a compound which irreversibly blocks alpha 1B receptors, completely blocked the phenylephrine-induced increase in c-fos mRNA. RNase protection experiments demonstrated that rat aorta prominently expressed mRNA for alpha 1B and alpha 1A/D receptors. Phenylephrine-induced c-fos mRNA was partially inhibited by H-7, a protein kinase C inhibitor, and by nifedipine, a Ca2+ channel blocker; these two compounds together had additive effects. In situ hybridization showed that expression of c-fos mRNA induced by phenylephrine was localized to aorta's medial layer. These results suggest that alpha 1 receptor-induced increase in c-fos mRNA in aorta is mediated by a chloroethyl-clonidine-sensitive receptor subtype signaling via increasing intracellular Ca2+ concentrations and activating protein kinase C.
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PMID:Alpha 1 adrenergic receptor-induced c-fos gene expression in rat aorta and cultured vascular smooth muscle cells. 804 Feb 63

Recent results suggest that insulin-like growth factor-I (IGF-I) may be involved in the transition of a hemodynamic load into cardiac hypertrophy and that the expression of IGF-I seems to be coupled to increased wall stress. The present study investigated the role of growth hormone (GH) and IGF-I in myocardial hypertrophy induced by volume overload. An aortocaval fistula (ACF) was created in male Wistar rats, and experiments were performed 2, 4, and 7 days after the onset of volume overload. Right and left ventricular (RV and LV, respectively) myocardial expression of GH receptor mRNA and IGF-I mRNA were quantitated by a solution hybridization RNase protection assay. RV GH receptor mRNA content was elevated on the fourth and seventh days after the induction of the shunt, with peak levels (0.63 +/- 0.16 versus 0.14 +/- 0.03 amol/microgram DNA for the sham-operated animals; P < .01) after 4 days. Similarly, IGF-I mRNA was significantly increased in the RV of shunted animals (1.26 +/- 0.13 versus 0.56 +/- 0.05 amol/micrograms DNA; P < .01) 7 days after surgery. In the left ventricle, where systolic pressure was reduced in ACF rats, no differences could be detected in GH receptor and IGF-I mRNA content between ACF and sham-operated rats on any of the experimental days. There was no difference in the ratio of RV to LV weight during the experimental period. We have shown that the thin-walled right ventricle responds to volume overload with an increase of GH receptor mRNA content followed by elevated expression of IGF-I mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jun
PMID:Increased expression of growth hormone receptor mRNA and insulin-like growth factor-I mRNA in volume-overloaded hearts. 820 22

alpha 1-Adrenergic receptors play important roles in mediating a wide range of important cellular responses; regulation of expression of these receptors may have pathophysiological significance in diseases such as hypertension. In order to pursue understanding of mechanisms involved in the regulation of expression of alpha 1 receptors, the effects of protein synthesis inhibitor cycloheximide on alpha 1B receptor gene expression were examined in DDT1 MF-2 smooth muscle cells. Cycloheximide markedly induced accumulation of the alpha 1B receptor mRNAs in a concentration- and time-dependent manner as detected by Northern blotting assays. The increased accumulation of alpha 1B receptor mRNA could be detected at 1 hr (1.7 +/- 0.2-fold) and the maximal accumulation occurred at 6 hr (5.4 +/- 0.3-fold, p < 0.01). Nuclear runoff assays reveal that cycloheximide markedly increased the transcriptional rate of the alpha 1B receptor gene. The stability of alpha 1B receptor mRNAs measured by RNase protection assays was essentially unchanged by cycloheximide. Incubation of DDT1 MF-2 cells with two additional protein synthesis inhibitors, anisomycin and emetine, had similar effects to those of cycloheximide. However, a further inhibitor, puromycin, did not induce alpha 1B receptor mRNAs when protein synthesis was almost completely inhibited. Furthermore, puromycin did not inhibit the capacity of cycloheximide to induce transcription of the alpha 1B receptor gene. These observations suggest that cycloheximide induces alpha 1B receptor gene expression through direct activation of gene transcription rather than inhibition of protein synthesis.
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PMID:Cycloheximide induces the alpha 1B adrenergic receptor gene by activation of transcription in DDT1 MF-2 smooth muscle cells. 826 46

We have previously demonstrated specific insulin-like growth factor I (IGF I) mRNA transcripts in cultured endothelial and vascular smooth muscle cells and postulated an important role for IGF I in blood vessel growth responses. The purpose of this study was to characterize IGF I gene expression in a model of aortic coarctation hypertension in the rat. This high-renin model of hypertension is associated with hyperplastic vascular responses. Northern analysis of rat aorta demonstrated four specific IGF I mRNA transcripts sized 7.6, 4.6, 1.8, and 0.9-1.2 kb. Quantitation of aortic IGF I mRNA levels by solution hybridization/RNase protection assay demonstrated induction of IGF I transcripts in the hypertensive aorta; levels more than doubled at 7 days and were still significantly elevated 21 days after coarctation. In situ hybridization analysis indicated that IGF I transcripts were localized primarily to adventitial surfaces in normotensive aorta, with minimal signal detected over vascular cells. In hypertensive aortas, there was an increase in IGF I transcripts primarily over vascular smooth muscle cells. Thus, vascular IGF I gene expression is induced in this model of high-renin hypertension. IGF I may play an important role in autocrine/paracrine-mediated vessel wall remodeling in hypertension.
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PMID:Abdominal coarctation increases insulin-like growth factor I mRNA levels in rat aorta. 841 83

Although several alpha-adrenergic receptor genes are expressed in the rat kidney, their expression in the renal vasculature has not been studied. Since pharmacological studies have suggested that an alpha 1B-adrenergic receptor may mediate renal vasoconstriction, we studied the expression of alpha 1B-adrenergic receptors in renal microvessels, from 10- to 14-week-old male spontaneously hypertensive rats (SHR) and their normotensive control, the Wistar-Kyoto rat (WKY). In these microvessels, isolated by perfusion with iron, alpha 1B-adrenergic receptor mRNA levels (by ribonuclease protection assay) were similar in SHR and WKY rats. Photo-affinity labeling with [125I]-arylazidoprazosin demonstrated the presence of alpha 1B-adrenergic receptor protein. Maximum receptor density (determined by 3H-prazosin binding: Bmax 59.8 +/- 4.1 and 58.7 +/- 4.3; Kd 0.48 +/- 0.05 nM and 0.31 +/- 0.06 nM in SHR and WKY, respectively) and chloroethylclonidine (CEC)-sensitive binding sites (determined by [125I]-(2-beta(4-hydroxyphenyl)-ethylaminomethyl)-tetralone binding) (125I-HEAT) were similar in SHR and WKY rats. There are two novel findings in these studies: (1) the alpha 1B-adrenergic receptor gene is expressed in renal microvessels of WKY and SHR; (2) alpha 1B-adrenergic receptor gene expression in renal microvessels is not altered in adult SHR. The failure to down-regulate expression of the alpha 1B-adrenergic receptor at the mRNA and protein level in the SHR could result in persistence of alpha 1B-adrenergic receptor effects and contribute to the increased vascular resistance in hypertension.
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PMID:Alpha 1B-adrenergic receptors in rat renal microvessels. 854 97

To elucidate the regulation of very-low density-lipoprotein (VLDL) receptor, we have studied its gene expression in the heart of spontaneously hypertensive rats-stroke prone (SHR-SP, an animal model for hypertension-induced cardiac hypertrophy) compared with Wistar-Kyoto rats. RNase protection assay showed that ventricular VLDL receptor mRNA falls to 41% of normal levels at 4 weeks when hypertension is not yet fully developed, and drops further to 14% at 13 weeks, when cardiac hypertrophy is established. Lipoprotein lipase mRNA decreases in parallel with VLDL receptor mRNA. In cultured neonatal rat ventricular cardiomyocytes, VLDL receptor mRNA decreases in parallel with the process of cardiocyte hypertrophy during the 24 hours after treatment with 10-8 mol/L endothelin-1, falling to 40% of the initial value. These results demonstrate that there is downregulation of VLDL receptor gene expression in cardiac hypertrophy both in vivo and in vitro and suggest that the regulation of the VLDL receptor is possibly linked with the switch in energy substrate from lipid to glucose known to occur in cardiac hypertrophy.
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PMID:Regulation of very-low-density lipoprotein receptor in hypertrophic rat heart. 860 9


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