Vascular sensitivity and reactivity to norepinephrine in diabetes mellitus

Vascular sensitivity (VS) and reactivity (VR) of hindquarters, totally isolated from rats made diabetic with 45 mg/kg of streptozotocin (STZ), were determined at 1, 2, 4, 8, and 12 wk post-STZ. Age-matched controls received saline injections and were followed for comparable periods. The hindquarters were perfused at constant flow (8-10 ml/min) with a Tyrode-perfluorocarbon (FC-43)albumin-alpha-globulin solution gassed with 95% O2-5% CO2. Tissues were continuously weighed and venous pressure adjusted to maintain an isogravimetric condition. VS and VR were determined from norepinephrine (NE) dose-response curves generated by infusing stock NE (1 mg/ml) at progressively increasing rates (0.004-0.025 ml/min) into a constant tissue perfusion rate (8-10 ml/min) for sufficient time to reach a plateau (2-3 min). Delivered doses ranged from 0.4 to 2.5 micrograms/ml. VR was established as the perfusion pressure reached in response to 2.5 micrograms/ml NE (Pmax). VS was defined as the delivered NE dose that increased perfusion pressure to 50% of Pmax (ED50). VS increased slightly but significantly (P less than 0.01) by 1 wk post-STZ and remained above control throughout the 12-wk post-STZ period. VR also increased significantly (P less than 0.05) by 1 wk post-STZ and remained above control throughout the 12-wk post-STZ period.