Calcium-Independent Release of Endothelial Nitric Oxide in the Arteriolar Network: Onset During Rapid Juvenile Growth

• Published in: Microcirculation (New York, N.Y. 1994) N.Y. 1994), 2004-09, Vol.11 (6), p.453-462
• Main Authors: NURKIEWICZ, TIMOTHY R., BOEGEHOLD, MATTHEW A.
• Format: Article
• Language: English
• Subjects: Animals; Arterioles; Blood Pressure - drug effects; Calcimycin - pharmacology; Calcium Signaling - drug effects; endothelium; Endothelium, Vascular - metabolism; Enzyme Inhibitors - pharmacology; Ionophores - pharmacology; juvenile growth; Male; microvascular control; Muscle, Skeletal - blood supply; Muscle, Skeletal - growth & development; nitric oxide; Nitric Oxide - blood; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type III; omega-N-Methylarginine - pharmacology; Rats; Rats, Sprague-Dawley; Simvastatin - pharmacology; Stress, Mechanical; Vascular Endothelial Growth Factor A - pharmacology; Vasodilation - drug effects
• ISSN: 1073-9688; 1549-8719
• DOI: 10.1080/10739680490475999

Objective: In young rats, skeletal muscle arterioles respond to acetylcholine, which elicits Ca2+-dependent endothelial nitric oxide (NO) release, but not to shear stress, which does not require increased intracellular Ca2+ for endothelial NO release. The aim of this study was to determine if, in general, signaling pathways for endothelial NO release that differ in their reliance on Ca2+ may be developing at different times during normal arteriolar network growth in skeletal muscle. Methods: Arteriolar responses to intraluminal infusion of the Ca2+ ionophore A23187, and the Ca2+-independent agonists vascular endothelial growth factor (VEGF) and simvastatin, were studied before and during NO synthase (NOS) inhibition with NG-monomethyl-L-arginine (L-NMMA) in the exteriorized spinotrapezius muscle of weanling (age 4-5 wks) and juvenile (7-8 wks) rats. Results: There were no age-dependent differences in arteriolar responses to A23187 applied over a concentration range that dilated arterioles from 9 ± 2 to 74 ± 8% of maximum, and L-NMMA attenuated these responses by the same amount in both age groups. In juveniles, arterioles dilated up to 39± 5% of maximum in response to VEGF, and up to 83 ± 6% of maximum in response to simvastatin, with L-NMMA greatly reducing the responses to both agonists. In contrast, arterioles in weanlings did not dilate in response to either agonist. Conclusions: These findings suggest that some Ca2+-independent signaling pathways for endothelial NO release may not initially be operational in the arteriolar network, but quickly become established during juvenile growth. This is consistent with the idea that microvascular control mechanisms are not fixed at birth, but rather undergo progressive changes in concert with microvascular network growth and changes in tissue metabolic requirements.