Developmental differences in response of mesenteric artery to acute hypoxia in vitro

Studies were conducted to determine if the response of in vitro mesenteric artery from 3- and 35-day-old swine to acute hypoxia was age dependent. Isometric tension developed by mesenteric artery rings was measured using a standard myograph apparatus. When the buffer aeration gas was changed from 95% O-2-5% CO2 to 95% N-2-5% CO2, phenylephrine-precontracted rings from both age groups consistently demonstrated a triphasic response, consisting of, in order, an initial, brief dilation, a sharp contraction, and a sustained loss of tone. The only portion of the triphasic response that was age dependent was the constrictor response, hypoxic vasoconstriction (HVC), which was significantly greater in rings from younger animals. HVC appeared to be mediated by a hypoxia-induced loss of constitutive nitric oxide production. Thus HVC was eliminated by endothelial removal, significantly attenuated by pretreatment with N-G-monomethyl-L-arginine (L-NMMA), but not with N-G-monomethyl-D-arginine, restored by coadministration of L-arginine, and accentuated by pretreatment with superoxide dismutase. Blockade of endothelin A receptors with BQ-610 or inhibition of cyclooxygenase or lipoxygenase activities with indomethacin or phenidone had no effect on HVC in either group. HVC appeared to be dependent on reduction in P-O2, not on reduced ATP secondary to hypoxia, as it did not occur in rings administered 2,4-dinitrophenol, an agent that uncouples oxidative phosphorylation. The magnitude of HVC, which appears to be mediated by hypoxia induced supression of NO production, is greater in mesenteric artery from 3-day-old swine than from 35-day-old swine.