Exaggerated impact of ATP-sensitive K+ channels on afferent arteriolar diameter in diabetes mellitus

Experiments were performed to determine the involvement of ATP-sensitive K channels (K-ATP channels) in the renal afferent arteriolar dilation that o ccurs during the hyperfiltration stage of insulin-dependent diabetes mellit us (IDDM). IDDM was induced in rats by streptozotocin (STZ) injection, and adequate insulin was provided to maintain moderate hyperglycemia. Sham rats received vehicle treatments. Two weeks later, efferent arteriolar function was assessed using the in vitro blood-perfused juxtamedullary nephron tech nique. Baseline afferent arteriolar lumen diameter was greater in STZ rats (25.9 +/- 1.1 mu m) than in sham rats (20.8 +/- 1.0 mu m). Glibenclamide (3 to 300 mu M) had virtually no effect on afferent arterioles from sham rats ; however, this K-ATP antagonist caused concentration-dependent afferent ar teriolar constriction in kidneys from STZ-treated rats, restoring lumen dia meter to 20.6 +/- 1.7 mu m (P > 0.05 versus sham baseline). In both groups of rats, pinacidil (a cyanoguanidine K-ATP agonist; 0.3 to 300 mu M) evoked concentration-dependent afferent arteriolar dilation, indicating the funct ional expression of K-ATP channels; however, lumen diameter was increased b y 73% in STZ kidneys but only by 48% in sham kidneys. The glibenclamide-sen sitive afferent arteriolar dilator response to 1 mu M PCO-400 (a benzopyran K-ATP agonist) was also accentuated in STZ kidneys. These observations sug gest that increases in both the functional availability and basal activatio n of K-ATP channels promote afferent arteriolar vasodilation during the ear ly stage of IDDM, changes that likely contribute to the etiology of diabeti c hyperfiltration.