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

1. Abnormal heat stress gene hsp70 expression has been demonstrated in organs as well as in cultured cells from spontaneously hypertensive rats and mice. 2. The polymorphism of hsp70, which is localized in the major histocompatibility complex, appears to segregate with a significant portion of hypertension. 3. Abnormal hsp70 expression may lead to anomalies in its feedback regulation, particularly since the steady state level of heat stress protein HSP70 seems to be lower in hypertensive than in normal animals. 4. Another biological consequence could be a modification of the effectiveness of cortisol, which may be involved in metabolic components of the pathogenesis of hypertension.
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PMID:Abnormal hsp70 gene expression: its potential key role in metabolic defects in hypertension. 144 10

Genetically hypertensive animals such as spontaneously hypertensive rats (SHR) and mice are more sensitive to thermal stress than normotensive controls. Genetic breeding experiments have demonstrated that the gene responsible for thermosensitivity segregates with an increase in blood pressure in the F2 generation and represents a genetic locus of hypertension. Due to a higher transcription rate of the heat shock protein 70 (hsp70) gene, which is a major heat stress gene, the accumulation of hsp messenger (m)RNA is increased in hypertension. Higher thermosensitivity and increased hsp mRNA accumulation are also observed in neonatal cardiomyocytes and cultured vascular smooth muscle cells from SHR, suggesting that these abnormalities are primary in character. This higher hsp70 transcription rate in hypertension could be due to an abnormality in the promoter region, to an interaction between heat stress trans-acting factor and heat stress element within the promoter of hsp70 or to an abnormal activation of heat stress trans-acting factor. A study using recombinant inbred animals has indicated that RT1 complex gene(s), a major histocompatibility complex in the rat, may be involved in the development of hypertension. These findings, together with the fact that hsp70 is located in the major histocompatibility complex, suggest that hsp70 gene or associated genes within the RT1 complex are responsible for environmental control of the expression of hypertension.
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PMID:Heat stress genes in hypertension. 209 96

Acute heat exposure is more lethal to spontaneously hypertensive mice (SHM) than to normal mice, whereas chronic heat treatment appears to be more beneficial in SHM, in that it normalizes blood pressure. By genetic breeding experiments, we demonstrated that the gene responsible for thermosensitivity segregates with an increment of blood pressure in the F2-generation and represents a genetic locus of hypertension. The molecular response to heat characterized by the induction of heat stress genes is abnormal in hypertension. There is an earlier accumulation and decline of heat-stress proteins (HSP70) and their messenger (m) RNA following heat exposure in tissues obtained from hypertensive mice. Our results indicate that thermosensitivity is genetically linked with hypertension and characterized by an abnormality in the synthesis of stress proteins as well as in the expression of their mRNA following heat exposure, which implies that a genetic defect is present in response to environmental stress in spontaneous hypertension.
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PMID:Genetic and molecular characteristics of thermosensitivity in hypertension. 324 Dec 53

We previously demonstrated that restraint and pharmacological agents that activate sympathetic nervous system activity induce expression of the 70-kD heat shock protein (HSP70) in major blood vessels. The magnitude and rapidity in which HSP70 is induced in the aorta suggest that it may play a salient role in the mechanical properties of vascular smooth muscle. Other investigators have reported that HSP70 inducibility is increased in genetically hypertensive animals. In this report, we have investigated the effects of acute and chronic (8-week) exposure to restraint and restraint in the presence of a randomized intermittent air jet on the development of hypertension and the induction of HSP70 in the aorta and adrenal glands of normotensive adult male Sprague-Dawley rats. Acute restraint or air jet resulted in a fivefold to sixfold increase in aortic HSP70 mRNA expression. Chronic exposure to restraint reduced the HSP70 response to acute restraint. In contrast, no adaptation of the HSP70 response to acute air jet was observed in aortas of chronically air jet-treated rats. In adrenal glands, HSP70 expression was reduced after chronic restraint and air jet, indicating that in this tissue, adaptation occurs to both stressors. There was no difference in HSP70 expression in unstressed rats that had been chronically exposed to restraint or air jet in either adrenal gland or aorta. A significant increase (P < .05) in systolic blood pressure developed in air jet-treated animals (120 +/- 3 mm Hg) but not in restrained rats (107 +/- 2 mm Hg) compared with unstressed controls (106 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Blood pressure and heat shock protein expression in response to acute and chronic stress. 772 95

The heat shock (HS) response is remarkably conserved during evolution and is evoked under many conditions of stress. There are a number of ways in which this ubiquitous response may be important for the understanding of renal pathophysiology. Ischemia, toxin exposure, and oxidative stress induce this response. Several models of hypertension are associated with increased susceptibility to environmental stress and increased accumulation of heat shock protein mRNA. HSP70 polymorphism has been demonstrated when comparing normotensive and hypertensive rats. Heat shock proteins may play a role in renal diseases through their important involvement in immunological processes. Several observations point to a role of the heat shock response in systemic lupus erythematosus (SLE). Autoantibodies against HSP70 and ubiquitin are found in many patients with this disease. Autoantibodies against ubiquitin and ubiquitinated histone H2A are localized to the kidney glomerular basement membrane of SLE patients with active disease. A better understanding of the HS response may thus provide important insight into renal pathophysiology and may suggest paradigms for therapeutic interventions.
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PMID:Heat shock proteins and the kidney. 804 58

We have previously demonstrated that acute hypertension induces heat shock protein gene expression in rat arterial wall. Here we provide evidence that this induction is mediated through the activation of heat shock transcription factor 1 in response to high blood pressure. Rats subjected to restraint or immobilization stress displayed an acute elevation in systolic pressure accompanied by an increase in heat shock protein 70 mRNA expression. Consistent with the rapid time course of mRNA induction, an increase in binding activity to an oligonucleotide encompassing a consensus heat shock element sequence was seen in protein extracts from aorta of restrained rats as assessed with gel mobility shift assays. A similar increase in DNA binding activity was also observed in aortic extracts from rats treated with various hypertensive agents, including phenylephrine, angiotensin II, and vasopressin. That the DNA binding activity was attributed to heat shock factor 1 was shown through use of antibodies to the transcription factor that retarded the DNA-protein complexes in gel mobility supershift assays. Western blot analysis of heat shock factor 1 protein expression in aortic extracts showed a slower mobility form of the protein in hypertensive rats, indicative of an activated, presumably phosphorylated, form of the transcription factor. These findings support the view that heat shock factor 1 is responsible for induction of heat shock protein 70 in the arterial wall during acute hypertension, a response that is likely to play an important role in protecting arteries during hemodynamic stress.
Hypertension 1996 Jul
PMID:Activation of heat shock transcription factor 1 in rat aorta in response to high blood pressure. 867 64

1. Genetic, common household and non-familial environmental factors contribute about 33, 15 and 50% of blood pressure (BP) variance, respectively. Although usually considered to be additive, the environmental impact on the expression of hypertension may also interact with genetic components. Even factors such as gender and age may exert an additive (subtractive) or interactive effect. These interactions usually lead to phenotypic amplification. 2. In some instances, the environmental impact is allele-dependent (putative locus of salt-sensitivity), and there are other occasions when phenotypic expression may be environmentally dependent. Environmental temperature appears to be another environmental modifier of BP. 3. Increased sensitivity to this environmental factor has been observed in hypertension, and a locus of thermosensitivity segregates with BP in mice. Candidate genes of environmental susceptibility are proposed to include tumour necrosis factor and the heat shock protein (HSP) family. An abnormal accumulation of HSP27 and HSP70 messenger RNA has been described in rodent (mice, rat) models of hypertension as well as in human subjects. Segregation of the HSP27 and HSP70 polymorphism with BP has been determined in at least some crosses. 4. These candidate genes of environmental susceptibility may also be involved in determining heart weight in addition to BP.
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PMID:Environmental stress and genes of hypertension. 884 3

BACKGROUND: Restraint-stress and administration of drugs that precipitate hypertension induce heat-shock protein (HSP) expression in the aorta. The exact mechanism supporting this hypertension-related HSP response is unclear because HSP induction is blocked by receptor-selective and nonselective antihypertensive agents. METHODS AND RESULTS: To identify mechanisms contributing to the pharmacological/physiological regulation of the HSP response in cardiovascular tissues, we administered clonidine to awake and freely moving animals to determine its effect on HSP expression in vivo. Inconsistent with previous work, we found that clonidine produced a dose-dependent and transient increase in HSP70 mRNA levels in the aorta. No other tissue examined displayed an HSP response after clonidine administration. Clonidine-induced HSP expression was not restricted to the HSP70 family; HSP89alpha, HSP89beta, and HSP60 were also induced. Interestingly, no heat-shock element-binding activity was observed after clonidine administration, suggesting that unusual transcriptional regulatory mechanisms mediate this response. Yohimbine and nifedipine blocked HSP70 mRNA expression, whereas isoproterenol, mecamylamine, and reserpine had no effect. CONCLUSIONS: The functional consequence of HSP expression in cardiovascular tissues may be to alter the responsiveness of cells in these tissues to subsequent drug or stress exposures, thereby implicating the HSP response as an important component of cardiovascular homeostasis. If so, treatment of mammalian organisms with drugs capable of inducting selective HSP expression in vascular tissue may alter the progression of cardiovascular disease processes.
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PMID:Clonidine-Induced Heat-Shock Protein Expression in Rat Aorta. 1068 95

Various renal insults result in induction of heat shock protein (HSP) expression within the kidney. Some of the HSPs induced in that manner are postulated to have renoprotective effects via either chaperoning actions or antioxidative properties. We have previously reported that long-term angiotensin (Ang) II administration induces the expression of renal HSP32, also known as heme oxygenase-1 (HO-1). Here, we investigated the regulation of expression and localization of other HSPs, including HSP70, HSP25, and alphaB-crystallin, in the kidney of rats undergoing long-term administration of Ang II (0.7 mg. kg(-1). d(-1)). Immunoblot analysis demonstrated that Ang II increased renal expression of HSP70 and HSP25, as well as HO-1, but that expression of alphaB-crystallin was unaffected by this treatment. The Ang II-induced increase in renal HSP70 and HSP25 was dependent on the angiotensin type 1 receptor activation but not on hypertension per se. Immunohistochemistry revealed that HSP70 and HSP25 were expressed in the medullar regions and in the renal arterial wall in the kidney of control rats. After Ang II infusion, signals for HSP70, HSP25, and HO-1 proteins increased in intensity in the endothelium and medial smooth muscle of the renal artery. In addition, all of these HSPs were induced in proximal renal tubular epithelial cells from the same segments, suggesting that similar mechanisms are responsible for upregulating these HSPs. Our data show that Ang II infusion induces renal HSP70 and HSP25, as well as HO-1, and that Ang II can induce expression of these HSPs in renal cells in a pressor-independent manner.
Hypertension 2002 Jan
PMID:Regulation and localization of HSP70 and HSP25 in the kidney of rats undergoing long-term administration of angiotensin II. 1179 90

Whereas induction of the 70-kDa heat shock protein (HSP70) in the nucleus tractus solitarii (NTS), the terminal site in the brain stem for primary baroreceptor afferents, augments baroreceptor reflex (BRR) response, the underlying cellular and molecular mechanism is essentially unexplored. In Sprague-Dawley rats, we evaluated the hypothesis that HSP70 may potentiate BRR response by up-regulating the molecular synthesis and functional expression of glutamate receptors in the NTS. Animals subjected to brief hyperthermic heat shock (HS; 42 degrees C for 15 min) exhibited augmented expression of NR1 or NR2A subunit of N-methyl-D-aspartate (NMDA) receptors, GluR1 or GluR4 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors and KA1 subunit of kainate receptors in the NTS. Intriguingly, this up-regulation of glutamate receptors was preceded by an increase in HSP70 expression at the NTS. The HS-induced augmentation in responsiveness of barosensitive NTS neurons to transient hypertension or potentiation of BRR response was discernibly blunted by MK-801 or 6-cyano-7-nitroquinoxaline-2,3-dione. Bilateral microinjection into the NTS of an antisense hsp70 oligonucleotide (50 pmol) before HS significantly suppressed the induced expression of HSP70 or the increase in glutamate receptor subunits in the dorsal medulla and discernibly attenuated the potentiation of BRR response. Control microinjection into the NTS of sense or scrambled hsp70 oligonucleotide (50 pmol) was ineffective. These findings suggest that HSP70 induced by HS may enhance BRR response by up-regulating the molecular synthesis and functional expression of NR1 or NR2A subunit of NMDA receptors and GluR1, GluR4, or KA1 subunit of non-NMDA receptors in the NTS.
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PMID:Up-regulation of glutamate receptors in nucleus tractus solitarii underlies potentiation of baroreceptor reflex by heat shock protein 70. 1196 Nov 27


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