AGI Apr. 39/4

Taylor, Mark S., Hong Gao, Jason D. Gardner, and Joseph N. Benoit. Effects of IBMX on norepinephrineinduced vasoconstriction in small mesenteric arteries. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G909–G914, 1999.—The present study assesses the effects of the phosphodiesterase inhibitor IBMX on norepinephrine (NE)-induced constriction of small mesenteric arteries. Arteries (,150 μm) were dissected from rats and mounted on a wire myograph for isometric force measurement. NE concentration effect curves were generated after exposure to 500 μM IBMX for 60 min. IBMX significantly reduced NE-induced tension development. Studies were also conducted following sarcoplasmic reticulum (SR) depletion (ryanodine, 10 μM) or L-type Ca21 channel blockade [(1)-BAY K 8644, 10 μM] in the presence and absence of IBMX. Both SR depletion and L-channel blockade reduced NE-induced tension generation, consistent with incomplete Ca21 mobilization. IBMX significantly attenuated NE responses in ryanodine and (1)-BAY K 8644-treated vessels. Finally, treatment of NE-stimulated vessels with IBMX (500 μM) caused a reduction in vascular tension that was greater than the concomitant reduction in cytosolic Ca21 concentration ([Ca]i), indicating that a portion of the IBMXmediated relaxation is Ca21-independent. These data suggest that IBMX attenuation of NE responsiveness not only involves a reduction in [Ca]i but also a significant decrease in Ca21 sensitivity.