Growth-dependent changes in endothelial factors regulating arteriolar tone

• Published in: American journal of physiology. Heart and circulatory physiology 2007-01, Vol.292 (1), p.H207-H214
• Main Authors: Samora, Julie Balch, Frisbee, Jefferson C, Boegehold, Matthew A
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological - physiology; Animals; Arterioles - growth & development; Arterioles - metabolism; Cardiology; Endothelium, Vascular - physiology; Human growth; In Vitro Techniques; Intercellular Signaling Peptides and Proteins - metabolism; Male; Muscle, Skeletal - blood supply; Muscle, Skeletal - growth & development; Nitric oxide; Rats; Rats, Sprague-Dawley; Rodents; Vasoconstriction - physiology; Veins & arteries
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00677.2006

Department of Physiology and Pharmacology and Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, West Virginia Submitted 26 June 2006 ; accepted in final form 18 August 2006 Previous studies from this laboratory suggest that during maturation, rapid microvascular growth is accompanied by changes in the mechanisms responsible for regulation of tissue blood flow. To further define these changes, we studied isolated gracilis muscle arterioles from weanling ( 25 days) and juvenile ( 44 days) Sprague-Dawley rats to test the hypothesis that endothelial mechanisms for the control of arteriolar tone are altered with growth. Responses to the endothelium-dependent dilator acetylcholine (ACh) were greater in weanling arterioles (WA) than in juvenile arterioles (JA), whereas there were no consistent differences between age groups in arteriolar responses to other endothelium-dependent agonists (A-23187, vascular endothelial growth factor, and simvastatin). Inhibition of nitric oxide synthase (NOS) with N -nitro- L -arginine methyl ester ( L -NAME) attenuated ACh-induced dilation in JA but not in WA. In JA, combined inhibition of NOS and cyclooxygenase (with indomethacin) reduced the dilator responses to ACh and simvastatin by 90% and 70%, respectively, but had no effect in WA. Cytochrome P 450 epoxygenase inhibition [with 2-(propargyloxyphenyl) hexanoic acid] had no effect on responses to ACh or simvastatin in either age group. Inhibition of Ca 2+ -activated or ATP-dependent potassium channels (with tetraethylammonium or glibenclamide, respectively) reduced these arteriolar responses in JA but not those in WA. These findings suggest that in fully grown microvascular networks, endothelium-dependent arteriolar dilation is mediated by the combined release of endothelial nitric oxide and vasodilator prostanoids, and in part through activation of Ca 2+ -activated and ATP-dependent potassium channels. However, during earlier microvascular growth, this dilation is mediated by other factors yet to be identified. This may have significant implications for the regulation of tissue perfusion during microvascular development. skeletal muscle microcirculation; endothelium; postnatal growth; nitric oxide; endothelium-derived hyperpolarizing factor Address for reprint requests and other correspondence: M. A. Boegehold, Center for Interdisciplinary Research in Cardiovascular Sciences, Robert C. Byrd Health Science