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.
BACKGROUND
We demonstrated recently that heat shock (HS)-induced heat shock protein 70 (HSP70) expression in bilateral nucleus tractus solitarii (NTS), the terminal site in the brain stem for primary baroreceptor afferents, confers cardiovascular protection against heatstroke by potentiating baroreceptor reflex (BRR) response. This study evaluated the hypothesis that altered regulation of HSP70 expression may be associated with the heightened susceptibility to heatstroke during hypertension.


RESULTS
Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats anesthetized with propofol were used. Compared with WKY rats, significant induction in HSP70 or phosphorylation of heat shock factor 1 (HSF1), but not HSF2, in the NTS and potentiation of BRR response in SHR occurred earlier (4 versus 8 hours), reaching peak magnitude sooner (16 versus 24 hours), and declined more rapidly after a brief hyperthermic HS (42+/-0.5 degrees C for 15 minutes). The protection conferred by HS against hypotension and bradycardia during the onset of heatstroke (45 degrees C for 60 minutes), although effective, was less effective in SHR. Microinjection bilaterally into the NTS of the selective protein kinase A (PKA) inhibitor H-89 (100 pmol) or the selective PKC inhibitor calphostin C (100 pmol) significantly attenuated all of the above events induced in SHR by HS. However, only H-89 was effective in WKY rats.


CONCLUSIONS
An altered temporal profile of HS-induced HSP70 expression or potentiation of BRR response by concurrent activation via both PKA and PKC pathways of phosphorylation of HSF1 in the NTS may be associated with greater susceptibility to heatstroke during hypertension.
Chan
Samuel H H
SH
Center for Neuroscience, National Sun Yat-sen University, Taiwan, Republic of China.
Wang
Ling-Lin
LL
Chang
Kuei-Feng
KF
Ou
Chen-Chun
CC
Chan
Julie Y H
JY
D000818:Animals; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D000076249:Heat Shock Transcription Factors; D018883:Heat Stroke / Q000503:physiopathology; D018869:Heat-Shock Response / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D008845:Microinjections; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C