Hypertension, aging, and myocardial synthesis of heat-shock protein 72.

Abstract

We determined the temperature-induced synthesis of the 72-kD heat-shock protein (hsp72) in hearts of normotensive and spontaneously hypertensive rats (SHR) subjected to whole-body hyperthermia (42.0±0.5°C for 15 minutes). The animals were studied at three diiferent ages: young (2 months), adult (6 months), and old (18 months). The hsp72 was determined by Western blot analysis using a monoclonal antibody. The results were calculated densito-metrically as a percentage of a commercial standard. Young SHR responded to hyperthermic stress with increased synthesis of hsp72 compared with age-matched normotensive rats (298.8 ±70.0% versus 88.3±25.5%). This trend was maintained in adult rats (118.1±31.0% A common feature of genetically hypertensive animals is a greater sensitivity to environmental temperature with respect to that of their normotensive control counterparts. 1-2 The increased thermosensitivity is genetically linked with hypertension 3 and at the molecular level is characterized by an over-expression of heat-shock proteins, 46 a group of highly conserved proteins synthesized during stress and involved in cellular protection. 712 Increased synthesis of the 72-kD heat-shock protein (hsp72) is a specific marker of the stress response in the heart as hsp72 is induced in the myocardium after heat treatment, ischemia, hemodynamic overload, or hypox-j a i3-i6 T n e synthesis of hsp72 in the myocardium of heat-shocked hypertensive animals has never been fully studied. This is particularly relevant because recently the induction of hsp72 synthesis has been shown to protect the myocardium against ischemia, 9 " 11 a pathological condition often associated with hypertension. During aging, the heart undergoes progressive functional alterations and becomes more vulnerable to isch-emic insult. 17 This is true of the hypertrophic heart of the spontaneously hypertensive rat (SHR). 18-19 Several studies show an age-dependent decrease in the expression of heat-shock protein in response to environmental stress in both isolated cell systems 20-21 and tissues. 22-23 The first aim of this study was to determine the synthesis of hsp72 in the heart of normotensive Wistar-Kyoto (WKY) rats and SHR subjected to whole-body hyperthermia. The second aim was to investigate the effects of aging on the synthesis of hsp72. versus 54.8±21.3%) but not in old rats (65.3±29.4% versus 43.6±15.1%). Aging caused a reduction of hsp72 expression in response to hyperthermic stress in both SHR (4.6-fold) and normo-tensive rats (twofold). These data show that hearts of young and adult SHR respond to heat shock with enhanced synthesis of hsp72. This abnormal response, attenuated by aging, is independent of the presence and degree of hypertension or hypertrophy and is potentially linked to the genetic determination of the disease. (Hypertension. 1994^4:620-624.) Key Words • heat-shock proteins • hypertension, essential • aging • heart Methods Animals The experiments were carried out in compliance with the Guide for the Care and Use of Laboratory Animals o...

Altered Temporal Profile of Heat Shock Factor 1 Phosphorylation and Heat Shock Protein 70 Expression Induced by Heat Shock in Nucleus Tractus Solitarii of Spontaneously Hypertensive Rats

“…25 Tissues from hypertensive animals manifest an increase in transcription rate and accumulation of hsp70 mRNA. 24,26 This enhanced expression of hsp70 gene seems to be transient, with a rapid decrease of hsp70 mRNA and protein levels in SHR. 26 Our present results additionally suggest that the temporal profile of HSF1 phosphorylation may be related to the altered HS-induced HSP70 expression and BRR potentiation in SHR.…”

Effect of Alzheimer Caregiving Stress and Age on Frailty Markers Interleukin-6, C-Reactive Protein, and D-Dimer

“…Most of these studies attempted to elevate HSP70 expression with a single hyperthermic stress (16)(17)(18)(19)(20)22,23) or acute exercise (20,21). If the attenuation were due simply to a decrease in the rate of synthesis, conceivably after several repeated stresses the protein would eventually increase to a level commensurate with the intensity of the stress.…”

“…Several studies conclude that HSP70 induction is impaired in the heart of aged animals following a variety of acute stresses including ischemia (15), heat (16)(17)(18)(19)(20), and exercise (20,21). An age-related decline in the HSP70 response has also been observed in a variety of other tissues including liver and skeletal muscle (22)(23)(24).…”

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