Determinants of terminal mesenteric artery resistance during the first postnatal month

Experiments were conducted to delineate the vascular effector systems that contribute to setting mesenteric vascular tone in swine during the first po stnatal month. Terminal mesenteric arteries (TMA), which function as resist ance vessels, were studied in vitro with a microvascular perfusion system a llowing independent pressure and flow manipulation. When pressure was varie d 0-100 mmHg in the absence of flow, TMA from 1-day-old animals demonstrate d myogenic vasoconstriction, whereas TMA from 40-day-old animals did not. I n 1- but not 40-day-old TMA, the endothelin A (ETA) receptor antagonist BQ- 610 shifted the pressure-diameter curve upward, whereas the ETB receptor an tagonist BQ-788 and the L-arginine analog N-G-monomethyl-L- arginine (L-NMM A) shifted the curve downward; in all instances, myogenic vasoconstriction was preserved. Flow eliminated myogenic vasoconstriction in 1- day-old TMA, i.e., diameter increased as a function of pressure. The effect of BQ-610 w as lost under flow conditions; however, BQ-788 and N-acyl-L-Trp-3,5-bis-( t rifluoromethyl) benzyl ester, an antagonist specific to the substance P neu rokinin-1 (NK1) receptor, shifted the pressure-diameter curve downward in t he presence of flow, whereas L-NMMA restored myogenic vasoconstriction. Add ing flow had no effect on the pressure-diameter relationship in 40-day-old TMA. Other blocking agents, including prazosin, losartan, indomethacin, and charybdotoxin, had no effect on the pressure-diameter relationship in eith er age group under flow or no-flow conditions. Constitutive production of n itric oxide (NO) and endothelin-1 participates in setting resistance in 1- day-old TMA, and important stimulants to NO production include flow and act ivation of ETB and NK1 receptors. In contrast, 40-day-old TMA act as passiv e conduits in which the elastic properties of the vessel are the primary de terminant of diameter.