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

In addition to its vasoconstrictor and aldosterone-stimulating action, angiotensin II also drives cell growth and replication in the cardiovascular system, which may result in myocardial hypertrophy and hypertrophy or hyperplasia of conduit and resistance vessels in certain subjects. These actions are mediated through angiotensin II receptors (subtype AT1), which activate the G protein, phospholipase C, diacylglycerol and inositol trisphosphate pathway, to increase the expression of certain protooncogenes (c-fos, c-myc and c-jun) and growth factors (platelet-derived growth factor-A-chain, transforming growth factor-beta 1 and basic fibroblast growth factor). The cellular responses to angiotensin II in vascular smooth muscle have been shown in different hypertensive vessels to be either hypertrophy alone, hypertrophy and DNA synthesis without cell division (polyploidy) or DNA synthesis with cell division (hyperplasia). In genetic hypertension, the altered structure of small arteries is due to either cellular hyperplasia or remodeling, whereas in renovascular hypertension there is hypertrophy of vascular smooth muscle cells. Angiotensin II also increases synthesis of some matrix components, activates blood monocytes and is thrombogenic. Angiotensin-converting enzyme (ACE) inhibitors prevent or reverse vascular hypertrophy in animal models of hypertension; this seems to be a class effect, shared to some extent with calcium channel blocking agents. In human hypertension, ACE inhibitors reduce the increased media/lumen ratio of large and small arteries in hypertension and increase arterial compliance. These properties are also shared by losartan, the first of the new class of angiotensin II receptor (AT1) antagonists. The clinical implications of these findings need to be tested through rigorous and prospective clinical trials.
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PMID:The renin-angiotensin system and vascular hypertrophy. 883 52

c-fos expression was analyzed by means of Fos-immunocytochemistry in the parabrachial (PB) nucleus of rats anesthetized and submitted to blood pressure or volume changes. The objective was to determine if neurons of the PB are differentially activated following increase or decrease of arterial pressure or blood volume. Hypertension or hypotension were induced by continuous intravenous infusion of phenylephrine hydrochloride or sodium nitroprusside, respectively. Changes in blood volume were induced by volume load caused by infusion of isotonic saline or hemorrhage. Both an increase and a decrease in blood pressure resulted in elevated levels of Fos-IR neurons in the central lateral, dorsal lateral, and external lateral (outer section) subnuclei of the PB. No Fos-IR cells were observed in the external medial, internal lateral and ventral lateral PB. Only occasionally we could see few Fos-immunoreactive (Fos-IR) neurons in the medial and superior lateral PB subnuclei. A very similar pattern of c-fos expression was seen after volume load or hemorrhage. Our results demonstrate that blood pressure or volume changes elicit c-fos expression in specific and apparently identical sets of neuron populations in the parabrachial nucleus. We conclude that these neurons, which seem to receive a stimulatory drive, are involved in the central neural control of both cardiovascular and blood volume regulation.
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PMID:c-fos expression in the parabrachial nucleus following cardiovascular and blood volume changes. 887 61

The prevalence of hypertension and atherosclerosis among subjects with hyperinsulinemia supports the premise of a direct metabolic link between insulin and angiotensin II at the cellular level. In the present study, the effect of insulin on the angiotensin II-induced growth of A10 smooth muscle cells (SMC) was investigated. Treatment of quiescent A10 cells with angiotensin II caused an increase in RNA synthesis, proto-oncogene c-fos mRNA levels and cell size dependent upon pretreatment with insulin. The insulin requirement was independent of its actions as a growth factor, since a pre-treatment of at least 24 h with insulin was essential for growth stimulation by angiotensin II. Using RT-PCR, insulin was shown to regulate AT2 receptor expression in both quiescent and differentiating cells. These data suggest the AT2 receptor, which mediates the growth effects of angiotensin II in A10 cells, may be the critical target for the effect of insulin.
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PMID:Insulin is required for angiotensin II-mediated hypertrophy of smooth muscle cells. 889 51

We investigated the physiologic role of Fos protein at the nucleus tractus solitarius (NTS) in the modulation of baroreceptor reflex (BRR) in adult, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infusion supplements). Repeated and scheduled activation of the baroreceptors by transient hypertension induced by i.v. administration of phenylephrine (2.5, 5.0 or 10.0 micrograms/kg) resulted in a significant increase in Fos-like immunoreactivity (Fos-LI), primarily in the caudal part of the NTS. This increase in Fos-LI in the barosensitive NTS neurons was appreciably reduced by bilateral microinjection into the caudal NTS of an antisense oligonucleotide (20 pmol, 20 nl) designed to target a region of the c-fos mRNA that flanks the initiation codon (5'-129 to 143-3'). The same treatment also discernibly enhanced the BRR response, but elicited no appreciable effect on systemic arterial pressure or heart rate. On the other hand, bilateral application to the NTS of the corresponding sense oligonucleotide (20 pmol, 20 nl) or an antisense cDNA (20 pmol, 20 nl) that targeted a different site of the c-.fos mRNA (5'-135 to 149-3') was ineffective. These results suggest that expression of the inducible c-fos gene in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibitory modulation of baroreflex control of blood pressure.
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PMID:Participation of Fos protein at the nucleus tractus solitarius in inhibitory modulation of baroreceptor reflex response in the rat. 894 25

The molecular mechanisms responsible for the vascular hypertrophy observed in the arteries of hypertensive subjects are poorly understood. In this study, we tested the hypothesis that an increase in intraluminal pressure could by itself induce some of the vascular changes associated with hypertension, such as increased DNA synthesis and c-fos expression. We perfused rat thoracic aortae at different pressures for up to 4 h. The perfusion system consisted of a peristaltic pump and a closed circuit of plastic tubing connected to a culture media bottle where rat thoracic aortae were placed. After a 30 min equilibration period at 20 mm Hg, the perfusion pressure was adjusted to "normotensive levels" (132 +/- 3/59 +/- 4 mm Hg) or "hypertensive levels" (204 +/- 5/74 +/- 8 mm Hg). 3H-Thymidine was added at this time. After 4 h, the arteries were removed from the apparatus. Tunica media and adventitia were separated and processed for scintillation counting. 3H-Thymidine incorporation was 39% higher in the "hypertensive" than in the "normotensive" arteries. In separate experiments, after a 20 min equilibration period, the arteries were perfused for an additional 30 min at 50/10, 100/35, or 150/50 mm Hg. After being removed from the perfusion apparatus, the arteries were homogenized and total RNA was isolated. c-fos Expression was analyzed by Northern blot. c-fos Expression corresponded directly with the perfusion pressure. The highest levels of c-fos expression were detected in the arteries exposed to the highest pressures. These findings support the hypothesis that hemodynamic and/or mechanical factors can influence cell growth and function.
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PMID:Increased intraluminal pressure induces DNA synthesis and c-fos expression in perfused rat aorta. 912 79

A semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay was used to examine ICE, c-fos, jun D and zif 268 mRNA expression in the aortic and renal artery of 12-month old SHRs and wistar rats. Using this assay system, it was observed that the levels of aortic and renal artery expression of ICE were markedly higher in SHRs than in wistar rats. In contrast, the aortic and renal artery expression of immediate early genes (IEGs), c-fos, jun D and zif 268, were significant lower in SHRs than in wistar rats. Thus, our results suggest that differential regulation of death gene ICE and IEGs such as c-fos, jun D and zif 268 might be involved in the mechanism of pathogenesis of hypertension.
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PMID:Induction of ICE and inhibition of c-fos, jun D and zif 268 in 12-month old spontaneously hypertensive rats. 921 81

Hypertension in the conscious rat, elicited by i.v. infusion of phenylephrine, evoked expression of the immediate early gene c-fos in discrete groups of brain stem neurons. Fos-immunoreactive neurons were located in the caudal ventrolateral medulla (CVLM); others were located in the nucleus of the tractus solitarius (NTS). Because of their sensitivity to alterations in arterial pressure, these neurons are likely to subserve the arterial baroreceptor reflex. The aim of this study was to identify the brain stem projections and the neurotransmitter content of the barosensitive CVLM neurons using neuronal tracing and immunohistochemistry. Some of the barosensitive CVLM neurons projected directly to the rostral ventrolateral medulla (RVLM), and many contained the GABA synthesizing enzyme, glutamic acid decarboxylase (GAD). Other CVLM neurons, containing markers of glutamate or catecholamine synthesis, were insensitive to baroreceptor stimulation. This study delineates neuronal pathways acting in the arterial baroreceptor reflex and identifies precisely GABA-synthesizing CVLM neurons as the source of inhibitory input to the RVLM.
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PMID:c-fos identifies GABA-synthesizing barosensitive neurons in caudal ventrolateral medulla. 933 8

Our previous in vivo studies (Hou et al. J Clin Invest. 1995;96:2469-2477.) demonstrated that chronic inhibition of nitric oxide synthase led to an exaggerated response to relatively low doses of angiotensin II, resulting in a rapid and marked cardiac fibrosis. To examine further the importance of angiotensin II in inducing cardiac fibrosis and the possibility that nitric oxide serves as a modulator of the proliferative effects of angiotensin II, we used cultured rat cardiac fibroblasts to study the interrelationships between these substances. Angiotensin II induced a delayed DNA synthetic response in quiescent cells that occurred 30 hours after exposure to the hormone. The most pronounced effect of angiotensin II on thymidine uptake occurred 36 to 42 hours after the addition to cells. This response was inhibited in a dose-dependent manner by the addition of either S-nitroso-N-acetylpenicillamine or sodium nitroprusside, each a source of nitric oxide. The nitric oxide donor was most effective in reducing thymidine incorporation when added 12 hours after angiotensin II, whereas the metabolite N-acetylpenicillamine had no effect at any time. The inhibitory effect of S-nitroso-N-acetylpenicillamine was mimicked by 8-bromoguanosine 3':5'-cyclic monophosphate but not by 8-bromoadenosine 3':5'-cyclic monophosphate. Nitric oxide donors did not appear to inhibit the induction of c-fos, Egr-1, or other immediate-early genes in response to angiotensin II. The results suggest that nitric oxide affects the cell cycle following the transition into G, and modulates the proliferation of fibroblasts during cardiac fibrosis induced by angiotensin II.
Hypertension 1997 Nov
PMID:Effect of nitric oxide on DNA replication induced by angiotensin II in rat cardiac fibroblasts. 936 52

The upregulation of left ventricular (LV) atrial natriuretic peptide (ANP) mRNA is a highly conserved marker of cardiac hypertrophy. The aim of this study was to further examine the pathway leading to ANP induction during pressure overload of the heart. Systolic wall stress was imposed acutely on isovolumetrically beating rat hearts in a Langendorff apparatus (sigma-=300 x 10[3] dyne/cm2). Northern and Western blots revealed that elevated wall stress induced LV c-fos and c-jun mRNAs (3.5- and 3-fold, P<.05 after 60 minutes), c-Fos and c-Jun proteins (3.9- and 4.3-fold, P<.05 after 120 minutes), as well as ANP mRNA (2.2-fold, P<.05 after 120 minutes). ANP upregulation was prevented by inhibition of protein synthesis (cycloheximide). Electrophoresis mobility shift assays were performed to link c-Fos and c-Jun (ie, components of the heterodimeric transcription factor AP-1) and ANP induction. A putative AP-1 binding site within the rat ANP promoter (nucleotides -512 to -473) bound specifically to nuclear proteins of wall stress-stimulated hearts. Antibodies directed against c-Fos protein resulted in a shift of this DNA/protein complex, suggesting physical interaction between AP-1 and the ANP promoter. Myocardial transfection of promoter constructs revealed that after acute imposition of wall stress, this AP-1 site enhanced a reporter gene (8- to 10-fold compared with a minimal promoter, P<.05). Interestingly, nuclear extracts of stimulated hearts as well as pure AP-1 protein bound to a putative CRE site (nucleotides -613 to -584) as well. Like the AP-1 site, this cAMP-responsible element (CRE) site was found to enhance the transfected ANP promoter/reporter gene significantly (17.5-fold, P<.05). Mutation of either AP-1 or CRE sites did not decrease reporter gene activity, whereas mutation of both resulted in loss of inducibility. These experiments suggest that LV ANP regulation after acute wall stress includes the activation of AP-1 and/or CRE cis acting elements. However, the transient nature of c-fos and c-jun upregulation also suggests that AP-1 is not the only mediator of ANP induction in LV hypertrophy.
Hypertension 1997 Dec
PMID:Regulation of the rat atrial natriuretic peptide gene after acute imposition of left ventricular pressure overload. 940 52

In situ expression of c-fos observed in response to phenylephrine (PE)-induced hypertension provided a basis for characterizing the organization and neurotransmitter specificity of neurons at nodal points of medullary baroreflex circuitry. Sustained hypertension induced by a moderate dose of PE provoked patterns of c-fos mRNA and protein expression that conformed in the nucleus of the solitary tract (NTS) to the termination patterns of primary baroreceptor afferents and in the caudal ventrolateral medulla (CVLM) to a physiologically defined depressor region. A majority of barosensitive CVLM neurons concurrently displayed markers for the GABAergic phenotype; few were glycinergic. Phenylephrine-sensitive GABAergic neurons that were retrogradely labeled after tracer deposits in pressor sites of the rostral ventrolateral medulla (RVLM) occupied a zone extending approximately 1.4 mm rostrally from the level of the calamus scriptorius, intermingled partly with catecholaminergic neurons of the A1 and C1 cell groups. By contrast, barosensitive neurons of the NTS were found to be phenotypically complex, with very few projecting directly to the RVLM. Extensive colocalization of PE-induced Fos-IR and markers for the nitric oxide phenotype were seen in a circumscribed, rostral, portion of the baroreceptor afferent zone of the NTS, whereas only a small proportion of PE-sensitive neurons in the NTS were found to be GABAergic. PE treatment parameters have been identified that provide a basis for defining and characterizing populations of neurons at the first station in the central processing of primary baroreceptor input and at a key inhibitory relay in the CVLM.
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PMID:Organization and transmitter specificity of medullary neurons activated by sustained hypertension: implications for understanding baroreceptor reflex circuitry. 941 14


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