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

Cardiac hypertrophy is largely due to cardiac fibroblast growth and increased synthesis of extracellular matrix. This study has investigated the contribution of the vasoactive hormone, angiotensin II, toward this hypertrophic process. We have demonstrated that cultures of adult rat cardiac fibroblasts express AT1 but not AT2 receptors for angiotensin II. The ability of angiotensin II to stimulate phosphoinositide catabolism and to elevate intracellular calcium concentrations in these cells was blocked by losartan, a specific AT1 receptor antagonist, but not by the AT2 receptor antagonist CGP 42112. Exposure of adult cardiac fibroblasts to angiotensin II resulted in the induction of several growth-related metabolic events including c-fos protooncogene expression and increased synthesis of DNA, RNA, and protein. Angiotensin II was also found to induce collagen type I, alpha 1 chain transcript expression in cardiac fibroblasts as well as the synthesis and secretion of collagen by these cells. The data demonstrate that angiotensin II, via AT1 receptors, can stimulate cardiac fibroblast growth and increase collagen synthesis in cardiac tissue. Thus, angiotensin II may contribute toward the development of cardiac hypertrophy in conditions of hypertension that are associated with elevated concentrations of angiotensin II.
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PMID:Characterization of angiotensin II receptors in cultured adult rat cardiac fibroblasts. Coupling to signaling systems and gene expression. 820 Sep 70

As a consequence of persistently raised blood pressure, left ventricular hypertrophy (LVH) develops as a compensatory mechanism for wall stress induced by the increase in afterload. Recent advances in the fields of molecular biology and genetics are now clarifying the mechanisms involved in the development of LVH. It has been reported that messenger RNA of oncogenes, such as c-fos and c-myc, increases by stretching; these oncogenes contribute to the progression of LVH, the messenger RNA expression of myosin and contractile protein synthesis in the cardiomyocytes. Vasoactive hormones and vascular contracting factors are also reported to have a progressive effect on LVH. In contrast, some antihypertensive agents have been shown to have pharmacological effects on regression of LVH in animals and man. The mechanisms responsible for LVH progression have been extensively studied. In contrast, the mechanisms of LVH regression have not been defined and require elucidation. This paper outlines the basic recognition of the mechanisms of LVH progression and discusses the varied pharmacological actions of calcium antagonists and angiotensin converting enzyme inhibitors on the regression of LVH in man and rats. Although the role of antihypertensive therapy in regression of LVH remains controversial, the calcium antagonist nicardipine appears to have an important role to play in the treatment of LVH in hypertension and in congestive heart failure.
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PMID:Therapeutic advances in the treatment of left ventricular hypertrophy. 837 Mar 75

We have identified and partially sequenced a soluble factor, myotrophin, from spontaneously hypertensive rat hearts and hypertrophic human hearts that enhances myocyte protein synthesis and stimulates myocardial cell growth. Our studies suggest that myotrophin may be a biochemical link between hemodynamic stress and myocardial cellular hypertrophy. When rat neonatal cardiac myocytes maintained in culture were incubated with myotrophin for 30 minutes, they showed a marked increase in c-myc, c-fos, and c-jun messenger RNA levels. Cardiac myocytes treated for 24 hours with myotrophin showed a fourfold increase in connexin 43 (gap junction protein), a sixfold increase in atrial natriuretic factor, a threefold increase in skeletal alpha-actin, and a threefold increase in total myosin transcript levels. Studies on myosin isoforms showed a selective increase in the beta-myosin heavy chain transcript levels but no reciprocal decrease in alpha-myosin heavy chain transcript levels. Our data suggested that myotrophin appears to be a primary modulator for myocardial cell growth and differentiation and may play an important role in the pathogenesis of cardiac hypertrophy. Myotrophin may be involved in the upregulation of myofibrillar protein and the activation of cardiac gene transcription during growth and hypertrophy of the myocardium, and the induction of early response gene expression may be linked to this response.
Hypertension 1993 Feb
PMID:Myotrophin induces early response genes and enhances cardiac gene expression. 842 77

Products of inositol lipid hydrolysis and levels of c-myc, c-fos and H-ras mRNAs were measured in rat left ventricle and vascular tissues 72 h and 9 days after the induction of aortic coarctation in order to examine inositol phosphate and proto-oncogene signals during the development of pressure-related cardiac and vascular structural changes. There was a significant increase in left ventricular and proximal aortic mass at both time points but no change in mesenteric resistance artery morphology in rats with coarctation. At 72 h there was a significant increase in c-myc, c-fos and H-ras mRNAs in the left ventricle of rats with coarctation, and this was accompanied by increased levels of inositol (1,4,5)-trisphosphate. Similar results were obtained in the proximal but not the distal aorta. In resistance arteries inositol phosphate production and proto-oncogene mRNA expression were unchanged. The results indicate that at 72 h aortic coarctation induced structural thickening in the left ventricle and proximal aorta and was associated with increased inositol phosphate production and stimulation of specific proto-oncogene mRNAs. By 9 days following surgery much of the structural change in these tissues was completed, and these raised cellular signals were no longer observed. The results suggest that both increased inositol lipid hydrolysis and a rise in the expression of these proto-oncogenes are important processes in the development of vascular hypertrophy seen in this model of hypertension.
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PMID:Effect of experimental hypertension on phosphoinositide hydrolysis and proto-oncogene expression in cardiovascular tissues. 843 67

The effect of hypertension on spinal induction of the c-fos proto-oncogene following noxious mechanical stimulation of the skin was studied in the rat. The occlusion of renal artery raised blood pressure steeply, reaching 52% over initial values. Oral administration of NG-nitro-L-arginine methyl ester provoked a gradual increase in blood pressure which reached up to 62%. The numbers of spinal dorsal horn Fos-immunoreactive nuclei were reduced to 66% and 38% of controls in animals with renal- and pharmacologically-induced hypertension, respectively. These data indicate that hypertension is accompanied by an inhibition of spinal nociceptive neurones which probably accounts for the hypoalgesia observed in hypertensive subjects. They further suggest an influence by the rate of increase of blood pressure on the level of spinal inhibition.
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PMID:Hypertension inhibits noxious-evoked c-fos expression in the rat spinal cord. 852 37

Previous studies have shown that angiotensin II (Ang II) can activate cardiovascular neurons within the medulla oblongata via an action on specific receptors. The purpose of this study was to determine the distribution of neurons within the medulla activated by infusion of Ang II into the fourth ventricle of conscious rabbits, using the expression of Fos, the protein product of the immediate early gene c-fos as a marker of neuronal activation. Experiments were done in both intact and barodenervated animals. In comparison with a control group infused with Ringer's solution alone, in both intact and barodenervated animals, fourth ventricular infusion of Ang II (4 to 8 pmol/min) induced a significant increase in the number of Fos-positive neurons in the nucleus of the solitary tract and in the rostral, intermediate, and caudal parts of the ventrolateral medulla. Double-labeling for Fos and tyrosine hydroxylase immunoreactivity showed that 50% to 75% of Fos-positive cells in the rostral, intermediate, and caudal ventrolateral medulla and 30% to 40% of Fos-positive cells in the nucleus of the solitary tract were also positive for tyrosine hydroxylase in both intact and barodenervated animals. The distribution of Fos-positive neurons corresponded very closely to the location of Ang II receptor binding sites as previously determined in the rabbit. The results indicate that medullary neurons activated by Ang II are located in discrete regions within the nucleus of the solitary tract and ventrolateral medulla and include, in all of these regions, both catecholamine and noncatecholamine neurons.
Hypertension 1996 Feb
PMID:Medullary neurons activated by angiotensin II in the conscious rabbit. 856 54

Previous work from this and other laboratories has demonstrated that the vasoconstrictor peptide angiotensin II results in hypertrophy of rat aortic smooth muscle cells that is associated with an increase in transcription of the early growth response gene c-fos. To explore the molecular mechanism responsible for c-fos induction in rat aortic smooth muscle cells, we used a series of reporter constructs linked to the chloramphenicol acetyl transferase gene in transient transfection experiments in rat aortic smooth muscle cells. Constructs containing both the serum response element and cAMP response element exhibited a 20-fold increase in chloramphenicol acetyl transferase activity in response to either serum or angiotensin II, whereas no increase was seen in vehicle-treated cells. Mutations in either the serum response element or cAMP response element alone, which have been demonstrated to inactivate these elements in other cell types, had no effect on chloramphenicol acetyl transferase inducibility. In contrast, if both elements were mutated, inducibility was almost abolished. Electrophoretic mobility shift assays with oligonucleotides corresponding to either serum response element or cAMP response element demonstrated that these oligonucleotides are capable of forming specific complexes with proteins from rat aortic smooth muscle cell nuclear extracts. One of the proteins binding to the serum response element is the previously described serum response factor, since it was supershifted by a monospecific antibody. These studies demonstrate that c-fox induction in smooth muscle occurs by a dual mechanism that can activate transcription via the serum response element or cAMP response element. These elements appear to act equally and independently, involving a distinct set of transacting factors.
Hypertension 1996 Jun
PMID:Multiple enhancer elements mediate induction of c-fos in vascular smooth muscle cells. 864 28

Hypotension- and hypertension-evoked expression of the protein product, Fos, of the immediate early gene c-fos was assessed throughout the rat brain as an approach for describing the neuronal populations that respond to alterations in arterial blood pressure. Conscious, chronically catheterized rats were treated with the vasoconstricting drug phenylephrine or the vasodilatating drug hydralazine to increase or decrease, respectively, arterial pressure by approx. 40 mm Hg for 90 min. Rats were then anesthetized, fixed by vascular perfusion, and sections representing the entire brain were processed for the immunocytochemical localization of Fos. In control rats treated with isotonic saline, few Fos-positive neurons were observed. In contrast, phenylephrine and hydralazine treatments resulted in different, yet reproducible, patterns of Fos expression in the brain, with hydralazine evoking Fos expression in more brain regions than phenylephrine. Brain regions containing Fos-positive neurons in rats treated with hydralazine included nucleus tractus solitarius, area postrema, caudal ventrolateral medulla, rostral ventrolateral medulla, bed nucleus of the stria terminalis, amygdala, paraventricular nucleus, supraoptic nucleus, subfornical organ and the Islands of Calleja. The nucleus tractus solitarius, paraventricular nucleus and the amygdala also contained Fos-positive neurons in phenylephrine-treated rats, although the number of Fos-positive neurons was always less than that noted in the hydralazine-treated rats and the location of Fos-positive neurons within these regions tended to differ between treatments. These results generally fit within an emerging understanding of brain circuitry underlying cardiovascular regulation.
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PMID:c-Fos expression in brain in response to hypotension and hypertension in conscious rats. 869 Aug 57

Neurons immunoreactive for Fos, the protein product of the immediate early gene c-fos, have been compared in the rostral ventral medulla and spinal cord of conscious normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) after baroreceptor unloading. Hypotension induced by a 60-minute intravenous infusion of sodium nitroprusside reduced baroreceptor activity; controls received intravenous saline. In WKY, 474 +/- 56 (n=6) Fos-positive neurons were identified in the rostral ventral medulla after nitroprusside infusion, a fivefold increase from controls; 50% of the tyrosine hydroxylase-containing neurons in the rostral ventral medulla were activated by this hypotension. Sympathetic preganglionic neurons, mainly sympathoadrenal neurons, were Fos positive after nitroprusside, but Fos-positive sympathetic preganglionic neurons were not observed in control WKY. In SHR, Fos immunoreactivity in the rostral ventral medulla was elevated in the control group compared with the WKY controls (236 +/- 31 and 93 +/- 15, respectively, n=6 for both). Nitroprusside hypotension did not further increase Fos immunoreactivity in the rostral ventral medulla, although the number of Fos-positive spinal sympathetic neurons increased. Our results have identified different neuronal activities between WKY and SHR in sites that are critical to sympathetic outflow. In WKY, nitroprusside effects are consistent with an activation of rostral ventral medulla neurons, including bulbospinal neurons, that are normally inhibited by baroreceptor activity. In SHR, basal nerve activity is increased, so even at rest, rostral ventral medulla neurons and sympathetic preganglionic neurons, mainly sympathoadrenal neurons, are Fos immunoreactive. These activated neurons are likely to contribute to the elevated blood pressure in this rat strain.
Hypertension 1996 Mar
PMID:Altered c-fos in rostral medulla and spinal cord of spontaneously hypertensive rats. 869 50

The immediate early genes c-fos and c-jun are transcription regulating factors. c-fos expression is widely used as a marker of neuronal activation and has been used in this study to identify those neurons, presumably vasomotor neurons, that are activated after interventions that alter blood pressure. c-fos and c-jun are expressed in the rostral ventral medulla (RVM) when the tonically active inhibitory inputs to the RVM are removed, either acutely or chronically, as in the SHR model of gentic hypertension. The injection of antisense oligonucleotide complementary to c-fos mRNA in the RVM attenuates the expression of c-fos, lowers resting blood pressure and attenuates blood pressure responses that are evoked via RVM mechanisms. These studies suggest a link between immediate early gene expression in neurons in the RVM and the regulation of blood pressure. c-fos could have an important role in regulating the activity of these central cardiovascular neurons. The role of the immediate early gene c-jun in cardiovascular control remains to be elucidated.
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PMID:Immediate early genes in blood pressure regulation. 874 21


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