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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 57; no. 3; pp. R767 - R776
• Main Authors: MARTINKA, Peter, FIELITZ, Jens, PATZAK, Andreas, REGITZ-ZAGROSEK, Vera, PERSSON, Pontus B, STAUSS, Harald M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.03.2005
• Subjects: Arterial hypertension. Arterial hypotension; Biological and medical sciences; Biomedical research; Blood and lymphatic vessels; Blood pressure; Cardiology. Vascular system; Effects; Experimental diseases; Fundamental and applied biological sciences. Psychology; Heart; Medical sciences; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Rodents; Vertebrates: nervous system and sense organs; Heart; Left; Variability; Cardiovascular disease; Activation; p38 kinase; p38 mitoger-activated protein kinase; Natriuretic hormone; sinoaortic baroreceptor denervation; Autonomic nervous system; Surgery; Blood pressure; Ventricular natriuretic peptide; Human; Hypertension; Glycoprotein; Rodentia; left ventricular end-diastolic pressure; transforming growth factor-beta 1; Vertebrata; Mammalia; Mouse; p125 focal adhesion kinase; Dysfunction; Baroreflex; Mechanotransduction; Circulatory system; Hemodynamics; Baroreceptor; Focal adhesion kinase; Denervation; Hypertrophy
• ISSN: 0363-6119; 1522-1490

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-1 (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. [PUBLICATION ABSTRACT]