Leukocyte adherence inhibits adenosine-dependent venular control of arteriolar diameter and nitric oxide.
Venular control of arteriolar perfusion has been the focus of several investigations in recent years. This study investigated 1) whether endogenous adenosine helps control venule-dependent arteriolar dilation and 2) whether venular leukocyte adherence limits this response via an oxidant-dependent mechanism in which nitric oxide (NO) levels are decreased. Intravital microscopy was used to assess changes in arteriolar diameters and NO levels in rat mesentery. The average resting diameter of arterioles (27.5 +/- 1.0 microm) paired with venules with minimal leukocyte adherence (2.1 +/- 0.3 per 100-microm length) was significantly larger than that of unpaired arterioles (24.5 +/- 0.8 microm) and arterioles (23.3 +/- 1.3 microm) paired with venules with higher leukocyte adherence (9.0 +/- 0.5 per 100-microm length). Local superfusion of adenosine deaminase (ADA) induced significant decreases in diameter and perivascular NO concentration in arterioles closely paired to venules with minimal leukocyte adherence. However, ADA had little effect on arterioles closely paired to venules with high leukocyte adherence or on unpaired arterioles. To determine whether the attenuated response to ADA for the high-adherence group was oxidant dependent, the responses were also observed in arterioles treated with 10(-4) M Tempol. In the high-adherence group, Tempol fully restored NO levels to those of the low-adherence group; however, the ADA-induced constriction remained attenuated, suggesting a possible role for an oxidant-independent vasoconstrictor released from the inflamed venules. These findings suggest that adenosine- and venule-dependent dilation of paired arterioles may be mediated, in part, by NO and inhibited by venular leukocyte adherence.
Dept. of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Min-ho
MH
Kim
Norman R
NR
Harris
D000241:Adenosine / Q000502:physiology*; D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004563:Electrochemistry; D066298:In Vitro Techniques; D036904:Leukocyte Rolling / Q000502:physiology; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008839:Microelectrodes; D018715:Microscopy, Video; D009569:Nitric Oxide / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D014699:Venules / Q000502:physiology*
D003497:Cyclic N-Oxides; D013113:Spin Labels; D009569:Nitric Oxide; D000243:Adenosine Deaminase; D000241:Adenosine; C001803:tempol