Streptozotocin-induced Diabetes Decreases Conducted Vasoconstrictor Response in Mouse Cremaster Arterioles

A conducted vasomotor response (CVR) is characterized by the spread of vasoconstriction or vasodilatation both up- and downstream from a local stimulation site in the microcirculation. It is believed to coordinate vasomotor responses within the microcirculation, and to contribute to the control of the major feed arteries to a given organ or tissue. Microvascular disease is a common and severe complication in diabetes, and we therefore studied CVR in streptozotocin (STZ) diabetic mice to examine whether changes in CVR might have a role in the pathophysiology of microvascular dysfunction in diabetes. The mouse cremasteric arterioles were stimulated locally with KCl and the resulting local response as well as conducted responses at 500 mum and 1000 mum were measured in control and STZ treated mice. Diabetes (n=8) induced by intraperitoneal injection of STZ in a dose of 100 mg/kg (mean blood glucose 16.8+/-2.1 mmol/l) decreased the conduction of vasoconstriction from 27.3+/-1.1% to 21.4+/-1.6% at 500 mum (p<0.01) and from 17.4+/-1.0% to 9.8+/-1.1% at 1000 mum (p<0.01) as compared with control (n=9). Treatment with either the protein kinase C beta II inhibitor (LY341684) or the oxygen radical scavenger tempol, did not improve the decreased conduction of vasoconstriction, but when administered together, the conduction of vasoconstriction was improved from 21.4+/-1.6% to 26.5+/-0.8% at 500 mum and 9.8+/-1.1% to 16.5+/-0.7% at 1000 mum (p<0.01). We conclude that STZ induced diabetes reduces conducted vasoconstriction to KCl in mouse cremasteric arterioles, and combined treatment with both an oxygen radical scavenger and a protein kinase C beta II inhibitor improves the reduced conducted vasoconstriction.