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)

Glucocorticoids mainly act through binding to cytosolic receptors that translocate to the nucleus after ligand binding, and dimerize to affect gene transcription in multiple fashions. The liganded receptors may interact with DNA at specific glucocorticoid responsive-elements, may physically hinder the ability of other transcription-regulating proteins to interact with their own DNA response-elements, and may form intranuclear complexes with the transcription factor c-jun, thus changing the number of c-jun/c-fos heterodimers that bind at AP-1 sites. By these, and perhaps other, mechanisms, physiologic concentrations of glucocorticoids regulate normal tissue metabolism, and supraphysiologic concentrations cause Cushing's syndrome. Cushing's syndrome leaves virtually no body tissue untouched. Left untreated, it results in progressive adiposity, myopathy, dermopathy (atrophy, stria, purpura, and hirsutism), psychopathy, glucose intolerance, hypercholesterolemia, hypertension, atherosclerosis, immunosuppression, and, ultimately, death. The physiology underlying each of these effects of hypercortisolism has been reviewed. The differences in the presentation of Cushing's syndrome in children and adults have also been discussed. The goal of the clinician must be to identify individuals with Cushing's syndrome as early in the course of the disease as possible so as to avoid the devastating complications that result from prolonged hypercortisolism. In patients for whom screening tests are equivocal, or only intermittently elevated, it may be necessary to re-evaluate the patient over time to establish that the patient has hypercortisolism. Some clinical guidelines for which patients to screen for hypercortisolism have been presented. Once hypercortisolism is established, patients with mild hypercortisolism (urine free cortisol less than four-fold above the upper limit of normal) should undergo tests to differentiate true Cushing's syndrome from a pseudo-Cushing state.
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PMID:Glucocorticoid action and the clinical features of Cushing's syndrome. 780 50

Pain arising from deep structures (muscles, joints, viscera) is the type of pain of most clinical relevance and also the type of pain about whose central representation we have the least knowledge. In contrast to cutaneous pain which evokes defensive behaviours, hypertension and tachycardia, the physiological reactions to most deep pain (especially if persistent) usually include quiescence, hypotension, bradycardia and decreased reactivity to the environment. Excitation of neurons within a discrete ventrolateral midbrain periaqueductal gray region evokes a reaction seemingly identical to that evoked by pain arising from deep structures. We report here, using the technique of the noxious stimulus-evoked expression of the immediate-early gene, c-fos, that neurons within this same ventrolateral periaqueductal gray region are selectively activated by a range of deep somatic and visceral nociceptive manipulations. Thus we have identified a specific brain region that both receives convergent, deep somatic and visceral nociceptive input, and which mediates the behavioural and physiological reactions characteristic of most deep pain.
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PMID:Convergence of deep somatic and visceral nociceptive information onto a discrete ventrolateral midbrain periaqueductal gray region. 783 71

To elucidate mechanisms of myocardial hypertrophy in spontaneously hypertensive rats (SHR), we examined by Northern blotting the expression of the proto-oncogenes c-myc, c-fos, c-sis, and c-fms in the hearts of 4- and 14-week-old SHR and normotensive Wistar-Kyoto (WKY) rats. No difference in c-myc or c-fos expression could be found between SHR and WKY rats. In SHR, c-sis gave a weak and c-fms a very strong signal at 14 weeks, whereas no signal for these oncogenes was found in either WKY rats or Sprague-Dawley controls. Since c-fms codes for the receptor of monocyte colony-stimulating factor, we next used in situ hybridization to localize the presence of c-fms in hearts of SHR at 14 weeks. We found strong signals for c-fms around small blood vessels and between cardiac myocytes in 14-week-old SHR but none in WKY rats. Immunohistochemical staining corroborated the presence of clusters of monocyte infiltration at these same perivascular sites in significantly greater numbers in SHR than in WKY rats. We conclude that c-fms expression and macrophage infiltration are increased in the perivascular space of hypertrophied hearts from SHR. We suggest that mononuclear cell recruitment and induction of c-fms may play a role in the development of hypertension-associated myocardial hypertrophy.
Hypertension 1995 Jan
PMID:Monocyte infiltration and c-fms expression in hearts of spontaneously hypertensive rats. 784 44

Brainstem catecholaminergic neurons have been implicated as mediating adaptive autonomic and neuroendocrine responses to cardiovascular challenges. To clarify the nature of this involvement, immuno- and hybridization histochemical methods were used to follow c-fos expression in these neurons in response to acute stimuli that differentially affect blood pressure and volume. From low basal levels, hypotensive hemorrhage (15%) provoked a progressive increase in the number and distribution of Fos-immunoreactive (ir) nuclei in the nucleus of the solitary tract (NTS), the A1 and C1 cell groups of the ventrolateral medulla, and in the pontine A5, locus coeruleus, and lateral parabrachial cell groups peaking at 2.0-2.5 hours after the challenge. Fos-ir ventrolateral medullary neurons, subsets of which were identified as projecting to the paraventricular hypothalamic nucleus or spinal cord, were predominantly aminergic, whereas most of those in the NTS were not. Infusion of an angiotensin II antagonist blunted hemorrhage-induced Fos expression in the area postrema, and attenuated that seen elsewhere in the medulla and pons. Nitroprusside-induced isovolemic hypotension yielded a pattern of c-fos induction similar to that seen following hemorrhage, except in the area postrema and the A1 cell group, where the response was muted or lacking. Phenylephrine-induced hypertension stimulated a restricted pattern of c-fos expression, largely limited to induced hypertension stimulated a restricted pattern of c-fos expression, largely limited to non-aminergic neurons, whose distribution in the NTS conformed to the termination patterns of primary baroreceptor afferents, and in the ventrolateral medulla overlapped in part with those of vagal cardiomotor and depressor neurons. These findings underscore the importance of brainstem catecholaminergic neurons in effecting integrated homeostatic responses to cardiovascular challenges and their ability to responding strategically to specific modalities of cardiovascular information. They also foster testable predictions as to effector neuron populations that might be recruited to respond to perturbations in individual circulatory parameters.
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PMID:Spatially and temporally differentiated patterns of c-fos expression in brainstem catecholaminergic cell groups induced by cardiovascular challenges in the rat. 784 57

The purpose of this study was to examine comprehensively and quantitatively the effects of sustained hypertension and hypotension on neuronal expression of Fos, the protein product of the proto-oncogene c-fos, in the brain of conscious rabbits. Hypertension or hypotension was produced by continuous intravenous infusion of phenylephrine or nitroprusside, at a rate sufficient to increase or decrease, respectively, arterial pressure by 20-30 mmHg, maintained for a period of 60 min. In comparison with a sham control group of rabbits that were infused with the vehicle solution alone, hypertension induced a significant increase in Fos immunoreactivity in the area postrema, the nucleus tractus solitarii, the caudal and intermediate ventrolateral medulla, the lateral parabrachial nucleus and the central nucleus of the amygdala. Double-labelling for tyrosine hydroxylase and Fos immunoreactivity showed that few (approximately 5%) of the Fos-positive neurons in the caudal and intermediate ventrolateral medulla in this group of animals were also positive for tyrosine hydroxylase. Hypotension also produced a significant increase in Fos immunoreactivity in the above regions, as well as in the rostral ventrolateral medulla, the A5 area, the locus coeruleus and subcoeruleus, the paraventricular nucleus, the supraoptic nucleus, the arcuate nucleus and the medial preoptic area. Approximately 65% of neurons in the rostral, intermediate and caudal ventrolateral medulla that expressed Fos following hypotension were also positive for tyrosine hydroxylase. Similarly, in the pons, approximately 75% of Fos-positive cells in the locus coeruleus, subcoeruleus and A5 area were positive for tyrosine hydroxylase. In the hypothalamus, 92% of Fos-positive neurons in the supraoptic nucleus, and 37% of Fos-positive neurons in the paraventricular nucleus, were immunoreactive for vasopressin. Our results demonstrate that hypertension and hypotension induce reproducible and specific patterns of Fos expression in the brainstem and forebrain. The distribution patterns and chemical characteristics of Fos-positive neurons following sustained hypertension or hypotension are significantly different. In particular, hypotension, but not hypertension, caused Fos expression in many tyrosine hydroxylase-positive cells within all pontomedullary catecholamine cell groups.
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PMID:Expression of Fos-like protein in brain following sustained hypertension and hypotension in conscious rabbits. 796 33

Heart disease in older individuals can be characterised as the result of 2 processes, hypertension and atherosclerosis, which are the major causes of heart failure in the elderly population. The aging heart undergoes changes at the molecular, cellular and organ levels. These age-related changes may then be modulated by pathological conditions, such as hypertension, and by the reduction of blood pressure. One characteristic of the aged heart is a limited capacity for adaptation, by hypertrophy, to increased mechanical load. This age-related attenuation of the hypertrophic response may be attributed to the diminished induction of proto-oncogenes such as c-fos, c-myc and c-jun. This diminution results from aging of the heart per se and may be modulated by extracardiac factors. With regard to the coronary vasculature, the age at which hypertension develops seems to be an important factor for determining the vascularity of hypertrophied hearts. Late-onset hypertension is not accompanied by coronary angiogenesis, and it decreases dilator reserve in spite of the absence of myocardial hypertrophy. In contrast, mechanical overload in infant hearts is accompanied by angiogenesis and normal dilator reserve. In principle, the normalisation of hypertension results in the regression of myocardial hypertrophy and decreased coronary dilator reserve. In aged hearts, it is not clear how hypertension-induced myocardial hypertrophy or coronary vascular changes regress. Although antihypertensive treatment is clearly associated with an improvement of cardiovascular mortality and morbidity in hypertensive elderly individuals, it remains unclear how treatments ameliorate the hypertension-induced alterations.
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PMID:Hypertension and age-related changes in the heart. Implications for drug therapy. 798 82

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

A role for humoral factors in the arterial hypertrophy accompanying hypertension has been suggested, but direct evidence is lacking. We measured [3H]thymidine incorporation of growth-arrested smooth muscle cells, cultured from renal preglomerular arterioles of normal rats and exposed for 12 h to 10% platelet-poor plasma-derived serum (PDS) from male rats with early, benign, one-kidney, one-clip hypertension and paired one-kidney normotensive control rats. In the presence of low background concentrations (1-2%) of fetal calf serum, PDS from hypertensive rats increased [3H]thymidine incorporation up to 117% more than PDS from normotensive rats (P < 0.0001). Results were similar for the < 10,000 mol wt fraction of PDS and for PDS from rats drinking saline vs. water or eating a 7% (high) vs. a 0.45% NaCl diet. PDS from hypertensive rats also differentially increased smooth muscle cell proliferation and c-fos mRNA expression. Platelet-derived growth factor levels in PDS were undetectable (< 0.17 ng/ml). This study provides evidence for altered concentrations of sodium chloride-unresponsive plasma factor or factors in hypertension that result in enhanced growth of arteriolar smooth muscle cells.
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PMID:Plasma-derived serum from hypertensive rats differentially increases growth of cultured arteriolar smooth muscle. 806 59

The administration of recombinant human erythropoietin (rHuEpo) to anemic chronic renal failure patients may be associated with an increase in blood pressure, possibly by direct effects on peripheral blood vessels. The experiments of the present study were designed to explore the hypothesis that rHuEpo might exert mitogenic effects on vascular smooth muscle cells (VSMCs), and that pre-existing hypertension might be a predisposing condition. Cultured aortic VSMCs from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied for DNA synthesis, phospholipase C activity, and cell growth related proto-oncogene expression in the presence of rHuEpo. In cells from both rat strains, rHuEpo dose-dependently increased DNA synthesis and stimulated phospholipase C activity, as indicated by 3H-thymidine incorporation and inositol phosphate formation, respectively. Exposure of VSMCs to rHuEpo for various periods gradually increased the levels of c-myc and JunB mRNAs and transiently induced c-fos mRNA expression as determined by Northern analysis. The hormone-induced DNA synthesis was markedly enhanced in VSMCs from SHR compared to those from WKY. In contrast, rHuEpo-induced phospholipase C activity and proto-oncogene expression did not differ between the two strains. Taken together, these results suggest that rHuEpo may function as a vascular smooth muscle cell growth promoting factor through activation of the phospholipase C cascade and a modulation of proto-oncogene expression. It could thereby contribute to vascular hypertrophy and arterial hypertension.
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PMID:Effect of erythropoietin on DNA synthesis, proto-oncogene expression and phospholipase C activity in rat vascular smooth muscle cells. 813 47

Recently ouabain has been shown to induce transcription of proto-oncogenes in different cell types. In the present study, we examined the effect of ouabain on the proliferation of cultured vascular smooth muscle cells (VSMCs). Primary aortic VSMCs of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and the rat VSMC cell line A10, were used. Different concentrations of ouabain (10(-9) to 10(-5) mol/L) were added to either quiescent or proliferating cells, and the cell number, the rate of thymidine incorporation into DNA, and the transcription of c-fos and c-myc were examined. The addition of ouabain to proliferating VSMC increased the rate of thymidine incorporation into DNA in a dose-dependent manner, and induced the transcription of the proto-oncogenes within 1 h. This latter response disappeared after 24 h. The number of cells significantly increased in response to low concentrations of ouabain (10(-8) to 10(-7) mol/L), but gradually decreased in response to higher concentrations of the agent, probably due to a toxic effect. Addition of ouabain to quiescent cells, in medium without serum, did not promote cell growth by any of the parameters examined. According to a current theory, endogenous digitalis-like substances possess natriuretic and hypertensive properties, and provide the link between an excessive intake of salt and high blood pressure. The mitogenic effect of ouabain on VSMCs may be a component of this hypertensive action.
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PMID:Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells. 813 13


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