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Am J Physiol Gastrointest Liver Physiol 276: G909-G914, 1999;
0193-1857/99 $5.00
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Vol. 276, Issue 4, G909-G914, April 1999

Effects of IBMX on norepinephrine-induced vasoconstriction in small mesenteric arteries

Mark S. Taylor, Hong Gao, Jason D. Gardner, and Joseph N. Benoit

Department of Physiology, University of South Alabama College of Medicine, Mobile, Alabama 36688

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 Ca2+ channel blockade [(+)-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 Ca2+ mobilization. IBMX significantly attenuated NE responses in ryanodine and (+)-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 Ca2+ concentration ([Ca2+]i), indicating that a portion of the IBMX-mediated relaxation is Ca2+-independent. These data suggest that IBMX attenuation of NE responsiveness not only involves a reduction in [Ca2+]i but also a significant decrease in Ca2+ sensitivity.

adenosine 3',5'-cyclic monophosphate; guanosine 3',5'-cyclic monophosphate; 3-isobutyl-1-methylxanthine; vascular smooth muscle; calcium


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