Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Mechanisms of blood pressure variability-induced cardiac hypertrophy and dysfunction in mice with impaired baroreflex

Item Type:Article
Title:Mechanisms of blood pressure variability-induced cardiac hypertrophy and dysfunction in mice with impaired baroreflex
Creators Name:Martinka, P. and Fielitz, J. and Patzak, A. and Regitz-Zagrosek, V. and Persson, P.B. and Stauss, H.M.
Abstract:Enhanced blood pressure variability contributes to left ventricular hypertrophy and end-organ damage, even in the absence of hypertension. We hypothesized that the greater number of high-blood pressure episodes associated with enhanced blood pressure variability causes cardiac hypertrophy and dysfunction by activation of mechanosensitive and autocrine pathways. Normotensive mice were subjected to sinoaortic baroreceptor denervation (SAD) or sham surgery. Twelve weeks later, blood pressure variability was doubled in SAD compared with sham-operated mice. Blood pressure did not differ. Cardiac hypertrophy was reflected in greater heart/body weight ratios, larger myocyte cross-sectional areas, and greater left ventricular collagen deposition. Furthermore, left ventricular atrial and brain natriuretic peptide mRNA expression was greater in SAD than in sham-operated mice. SAD had higher left ventricular end-diastolic pressures and lower myocardial contractility indexes, indicating cardiac dysfunction. Cardiac protein content of phosphorylated p125 focal adhesion kinase (p125 FAK) and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) was greater in SAD than in sham-operated mice, indicating activation of mechanosensitive pathways of cardiac hypertrophy. Furthermore, enhanced cardiac renin and transforming growth factor-beta1 (TGFbeta1) protein content indicates activation of autocrine pathways of cardiac hypertrophy. Adrenal tyrosine hydroxylase protein content and the number of renin-positive glomeruli were not different, suggesting that sympathetic activation and the systemic renin-angiotensin system did not contribute to cardiac hypertrophy. In conclusion, more frequent blood pressure rises in subjects with high blood pressure variability activate mechanosensitive and autocrine pathways leading to cardiac hypertrophy and dysfunction even in the absence of hypertension.
Keywords:Sinoaortic Baroreceptor Denervation, Transforming Growth Factor-Beta1, p125 Focal Adhesion Kinase, p38 Mitogen-Activated Protein Kinase, Left Ventricular End-Diastolic Pressure, Animals, Inbred C57BL Mice, Mice
Source:American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
ISSN:0363-6119
Publisher:American Physiological Society
Volume:288
Number:3
Page Range:R767-R776
Date:March 2005
Official Publication:https://doi.org/10.1152/ajpregu.00445.2004
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library