Repetitive hyperthermia attenuates progression of left ventricular hypertrophy and increases telomerase activity in hypertensive rats

Abstract

Repetitive hyperthermia attenuates progression of left ventricular hypertrophy and increases telomerase activity in hypertensive rats. Am J Physiol Heart Circ Physiol 302: H2092-H2101, 2012. First published March 16, 2012 doi:10.1152/ajpheart.00225.2011.-We investigated the hypothesis that repetitive hyperthermia (RHT) attenuates the progression of cardiac hypertrophy and delays the transition from hypertensive cardiomyopathy to heart failure in Dahl saltsensitive (DS) hypertensive rats. Six-week-old DS rats were divided into the following five groups: a normal-salt diet (0.4% NaCl) (NS group), a normal-salt diet plus RHT by daily immersion for 10 min in 40°C water (NSϩRHT group), a high-salt diet (8% NaCl) (HS group), a high-salt diet (8% NaCl) plus RHT (HSϩRHT group), and high-salt diet (8% NaCl) plus RHT with 17-DMAG (HSP90 inhibitor) administration (HSϩRHTϩ17-DMAG group). All rats were killed at 10 wk. Cardiac hypertrophy and fibrosis were noted in the HS group, whereas RHT attenuated salt-induced cardiac hypertrophy, myocardial and perivascular fibrosis, and blood pressure elevation. The phosphorylated endothelial nitric oxide synthase (eNOS) and Akt were decreased in the HS group compared with the NS group, but these changes were not observed in the HSϩRHT group. The levels of HSP60, 70, and 90 were elevated by RHT. Moreover, the increased levels of iNOS, nitrotyrosine, Toll-like receptor-4, BNP, PTX3, and TBARS in the HS group were inhibited by RHT. Telomeric DNA length, telomerase activity, and telomere reverse transcriptase (TERT) were reduced in the HS group; however, these changes were partially prevented by hyperthermia. In conclusion, RHT attenuates the development of cardiac hypertrophy and fibrosis and preserves telomerase, TERT activity and the length of telomere DNA in salt-induced hypertensive rats through activation of eNOS and induction of HSPs. cardiac hypertrophy; endothelial nitric oxide synthase; oxidative stress; telomere; heat shock protein HYPERTENSION IS ONE OF MAJOR risk factors responsible for cardiovascular disease and may lead to cardiac hypertrophy and diastolic heart failure (DHF). DHF is defined as heart failure with preserved left ventricular (LV) contraction and is characterized by abnormal relaxation and/or increased stiffness of the LV leading to impaired filling during diastole. Typically, diastolic function is evaluated by the E/A ratio using echocardiography. LV diastolic dysfunction is often manifested in individuals with hypertension. About 30 -40% of heart failure cases occur in patients with diastolic dysfunction and normal systolic function (28,36). Cardiac hypertrophy and resultant fibrosis develop as an adaptive response to pressure overload in hypertension and are commonly associated with DHF. Progressive cardiac remodeling characterized by LV hypertrophy, chamber enlargement, and pump dysfunction occurs in response to hypertension and is accompanied by progressive accumulation of the extracellular matrix (36).Hyperthermia using dry sauna improves cardiac functio...

Serum Heat Shock Protein 90 Alpha: A New Marker of Hypertension-Induced Endothelial Injury?

“…Moreover, Hsp-90α concentrations are higher in overweight or obese patients with newly diagnosed arterial hypertension than in overweight or obese patients with normal blood pressure. These observations are concordant with previous findings of increased Hsp-90 expression in animal models of hypertension [16][17][18][19][20]. It should be emphasized that there is as yet no data on Hsp-90α expression in human subjects with spontaneous hypertension.…”

“…The potential role of Hsp-90α in the development of arterial hypertension remains unclear, although several studies have been undertaken in an attempt to elucidate this relationship [16][17][18][19][20][21][22].…”

“…This phenomenon resulted from both induction of heat shock proteins (Hsp-90, Hsp-60 and Hsp-70) and activation of eNOS [17].…”

COA-Cl (2-Cl-C.OXT-A) can promote coronary collateral development following acute myocardial infarction in mice

“…Echocardiographic analysis was performed with an echocardiographic machine with a 15-MHz transducer (Toshiba, Japan) at 7 days after MI, as described previously 26 . From 2-dimensional short-axis imaging with the M-mode, left ventricular end-diastolic diameter (LVEDD) and end-systolic diameters (LVESD) were measured, and fractional shortening was calculated as {(LVEDD-LVESD)/LVEDD × 100 (%FS) as described previously 26 . The left ventricular ejection fraction (LVEF) was calculated using the formula EF% = [(LVEDV − LVESV)/LVEDV] × 100; where LVEDV and LVESV are left ventricular end-diastolic volume and left ventricular end-systolic volume, respectively.…”

“…We used the following primary antibodies: inducible nitric oxide synthase (iNOS) (#6 10432, 1:1000) (BD Transduction Laboratories, Lexington, KY), endothelial nitric oxide synthase (eNOS) (#9586, 1:1000), Phospho-eNOS (Ser1177) (#9570, 1:1000), MMP-9 (#3852, 1:1000) (Cell Signaling, Danvers, MA), β-actin I-19 (sc-1616, 1:1000), VEGF (A-20) (sc-152, 1: 200) (Santa Cruz Biotechnology, INC., Santa Cruz, CA), cleaved caspase-3 (CCP3) and nitrotyrosine (N0409, 1:1000) (Sigma-Aldrich, St. Louis, MO). Myocardial TBARS was measured as previously described (Cayman Chemical, Ann Arbor, MI) 26 .…”