REDUCED NA-K+ PUMP ACTIVITY IN DIABETIC RABBIT CAROTID-ARTERY - REVERSAL BY ALDOSE REDUCTASE INHIBITION()

This study addresses the question of whether a decrease in basal Na+ p ump [Na+-K+-adenosinetriphosphatase (ATPase)] activity occurs in the c arotid artery of an alloxan-diabetic rabbit and, if so, whether it is associated with altered Rb+-86 uptake and contractile response to ouab ain and K+-free solution. Ouabain-sensitive Rb-89+ uptake, an index of Na+ pump activity, was diminished approximately 50% in carotid arteri es from diabetic rabbits. Concurrent with this, contractions induced b y incubating the carotid arteries in a K+-free solution (in the absenc e of phentolamine) were significantly larger in the diabetic group. Re addition of K+ (1 mM) to arteries contracted with the K+-free solution caused relaxations that were slower to occur and of lesser magnitude in diabetic than in control rabbits. In contrast to the contractions c aused by the K+-free medium, contractions caused by incubation with ou abain (1 mM) in the presence of phentolamine were significantly smalle r in the diabetic group. Treatment of diabetic rabbits with an aldose reductase inhibitor, zopolrestat, at both high and low doses restored the alterations in vascular reactivity toward normal. The results indi cate that the Na+ pump activity is diminished in the carotid artery of diabetic rabbit, and this is associated with abnormal vascular respon siveness and increased polyol pathway flux.