Microvascular clearance of macromolecules in skeletal muscle of spontaneously diabetic rats.

Microvascular clearance of FITC-Dextran 150 (fluorescein isothiocyanate dextran, MW 150,000) was studied in cremaster muscles of control (BB/W-R) and diabetic (BB/W-DM) rats following daily injections of a full (FD) or a 1/2 (reduced; RD) dose of insulin. The cremaster muscle was placed in an intravital chamber and superfused with bicarbonate buffer (pH 7.4, equilibrated with 95% N2-5% CO2). A 1-hour period of stabilization was followed by the i.v. injection of FITC-dextran 150 and an equilibration period of 45 min. Suffusate samples were collected for 1 h for control measurements. Following this period, bradykinin was applied topically at a concentration of 10(-7) M. Samples were collected for a final hour for the assessment of clearance. The mean +/- SEM FITC-dextran 150 clearance values (microliter/60 min/g) for BB/W-R, BB/W-DM FD, and BB/W-DM RD were 11.5 +/- 1.8, 14.8 +/- 3.4, and 90.5 +/- 12.0, respectively. The corresponding values after topical application of 10(-7) M bradykinin were 23.7 +/- 5.9, 24.2 +/- 4.4, and 98.7 +/- 25.0. Our results indicate that bradykinin evokes a twofold increase in FITC-dextran 150 clearance in the BB/W-R (control) animals and in the BB/W-DM rats receiving full-dose insulin. In contrast, bradykinin does not further enhance the eightfold increase in FITC-Dextran 150 clearance observed in the reduced-insulin dose-treated BB/W-DM group. Thus, our data show that insulin, administered at a full dose, protects the functional integrity of microvascular perm-selectivity in diabetes mellitus.