Nitric oxide measurements in rat mesentery reveal disrupted venulo-arteriolar communication in diabetes.
OBJECTIVE
Arteriolar tone is partially controlled by diffusing mediators released by closely paired venules and is reported to depend on venular shear and venular leukocyte adherence. In healthy rat mesentery, venule-initiated arteriolar dilation and consequent enhanced capillary flow appear to be tightly regulated by nitric oxide (NO). In contrast, diabetes inhibits NO-dependent vasodilation and is associated with dysfunctional microcirculation. The objective of this study was to investigate venule-dependent NO in diabetes.


METHODS
Arteriolar and venular wall concentrations of NO were measured in control and diabetic (streptozotocin-induced) rat mesentery with fluorescent diaminofluorescein-2-diacetate (DAF-2-DA); tissue NO was measured with DAF-2. Venular leukocyte adherence and microvascular shear rates were also measured.


RESULTS
Microvascular NO in diabetic rats was found to be significantly lower (<50%) than in controls. In normal rats, arteriolar NO demonstrated a positive correlation with venular NO and venular shear, and a negative correlation with venular leukocyte adherence. Diabetes eliminated all these correlations. No correlation was present between arteriolar NO and arteriolar shear in either normal or diabetic rats.


CONCLUSIONS
Arteriolar NO appears to be enhanced by venular shear in normal but not in diabetic rats. This dysfunction could contribute to poor capillary perfusion in diabetes.
Department of Bioengineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Kavitha
K
Nellore
Norman R
NR
Harris
D000818:Animals; D001160:Arterioles; D002448:Cell Adhesion; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000737:chemistry; D018056:Hemorheology; D007962:Leukocytes / Q000502:physiology; D009569:Nitric Oxide / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation; D013311:Streptozocin; D014699:Venules
D009569:Nitric Oxide; D013311:Streptozocin