Effects of IBMX on norepinephrine-induced vasoconstriction in small mesenteric arteries.
The present study assesses the effects of the phosphodiesterase inhibitor IBMX on norepinephrine (NE)-induced constriction of small mesenteric arteries. Arteries ( approximately 150 micrometer) were dissected from rats and mounted on a wire myograph for isometric force measurement. NE concentration effect curves were generated after exposure to 500 microM IBMX for 60 min. IBMX significantly reduced NE-induced tension development. Studies were also conducted following sarcoplasmic reticulum (SR) depletion (ryanodine, 10 microM) or L-type Ca2+ channel blockade [(+)-BAY K 8644, 10 microM] 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 microM) 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.
Taylor
M S
MS
Department of Physiology, University of South Alabama College of Medicine, Mobile, Alabama 36688, USA.
Gao
H
H
Gardner
J D
JD
Benoit
J N
JN
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D012433:Ryanodine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine