Inhibition of leukocyte adherence enables venular control of capillary perfusion in streptozotocin-induced diabetic rats.
OBJECTIVE
Vasoactive molecules can diffuse from venules to dilate closely paired arterioles and enhance capillary perfusion. Venular control of capillary flow has been found to be dependent on nitric oxide (NO), which might be scavenged rapidly in diabetic microvasculature due to the presence of activated leukocytes. This study attempts to improve venular control of capillary flow using fucoidan, which inhibits venular leukocvte adhesion.


METHODS
Microvascular red blood cell velocity was measured in the mesentery of streptozotocin-induced diabetic rats, with and without fucoidan treatment, and in normal rats. Arteriolar pathways leading to branching capillaries were videotaped to measure the percent of the surrounding area occupied by a venule (% pairing). Microvascular wall NO was measured using fluorescent diaminofluorescein-2-diacetate in diabetic rats, with and without fucoidan treatment.


RESULTS
In normal rats, close pairing of venules to arterioles resulted in faster capillary flow. However, after 4-5 weeks of diabetes, the correlation between capillary velocity and % pairing was no longer significant. Capillary velocity and % pairing decreased approximately 50% in comparison to normal rats. Treatment of diabetic rats with fucoidan restored venular control of capillary flow and increased NO levels.


CONCLUSIONS
Leukocyte-derived mediators that scavenge NO may lead to inadequate venular control of capillary flow in diabetes.
Nellore
Kavitha
K
Department of Bioengineering, Pennsylvania State University, University Park, Pennsylvania, USA.
Harris
Norman R
NR
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D002196:Capillaries; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D004912:Erythrocytes; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000473:pathology*; D018715:Microscopy, Video; D009569:Nitric Oxide / Q000032:analysis; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013311:Streptozocin; D014699:Venules / Q000473:pathology / Q000502:physiology
D000925:Anticoagulants; D011134:Polysaccharides; D009569:Nitric Oxide; D013311:Streptozocin; C007789:fucoidan