Shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries

• Published in: Journal of applied physiology (1985) Vol. 98; no. 3; pp. 940 - 946
• Main Authors: Woodman, Christopher R, Price, Elmer M, Laughlin, M. Harold
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.03.2005; American Physiological Society
• Subjects: Aging - physiology; Animals; Arteries - cytology; Arteries - physiology; Biological and medical sciences; Blood Flow Velocity - physiology; Blood Pressure - physiology; Blood vessels; Circulatory system; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - physiology; Mechanotransduction, Cellular - physiology; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Muscular system; Nitric oxide; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type III; Rats; Rats, Inbred F344; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Shear Strength; Stress; Stress, Mechanical; Striated muscle. Tendons; Vasodilation - physiology; Vertebrates: osteoarticular system, musculoskeletal system; Rat; Enzyme; Rodentia; real-time polymerase chain reaction; Gene expression; Soleus muscle; Real time; endothelial dysfunction; Artery; Nitric-oxide synthase; Vasodilation; Endothelium; Polymerase chain reaction; Vasomotricity; Vertebrata; Mammalia; Messenger RNA; Dysfunction; Blood vessel; Shear stress; Circulatory system; Oxidoreductases
• DOI: 10.1152/japplphysiol.00408.2004
• ISSN: 8750-7587

Departments of Biomedical Sciences and Physiology and The Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri Submitted 15 April 2004 ; accepted in final form 28 October 2004 We tested the hypothesis that increased intraluminal shear stress induces endothelial nitric oxide (NO) synthase (eNOS) mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries (SFA) by increasing NO production. SFA were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats and cannulated with two resistance-matched glass micropipettes. SFA were exposed to no flow (NF), low flow (LF), intermediate flow (IF), or high flow (HF) for 4 h. Mean intraluminal shear stress ranged from 0 to 82 dyn/cm 2 . At the end of the 4-h treatment period, eNOS mRNA expression was assessed in each SFA. eNOS mRNA expression was significantly lower in old NF SFA than in young NF SFA. In old SFA, eNOS mRNA expression was induced by IF (+154%) and HF (+136%), resulting in a level of expression that was not different from that of young SFA. In a separate series of experiments, SFA were pretreated with NF or HF for 4 h, and endothelial function was assessed by examining vasodilator responses to ACh. ACh-induced dilation was less in old NF SFA than young NF SFA. Pretreatment with HF improved ACh-induced dilation in old SFA such that the response was similar to that of young SFA. In the presence of N -nitro- L -arginine to inhibit NOS, ACh-induced dilation was inhibited in old HF SFA such that the response was no longer greater than that of old NF SFA. These results indicate that increased intraluminal shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent SFA by increasing NO production. endothelium; gene expression; real-time polymerase chain reaction; endothelial dysfunction Address for reprint requests and other correspondence: C. R. Woodman, Dept. of Biomedical Sciences, Univ. of Missouri, W108 Veterinary Medicine, 1600 E. Rollins Rd., Columbia, MO 65211 (E-mail: woodmanc{at}missouri.edu )