Reduced Na-K pump but increased Na-K-2Cl cotransporter in aorta of streptozotocin-induced diabetic rat

The activities of Na-K-ATPase and NaK-2Cl cotransporter (NKCC1) were studie d in the aorta, heart, and skeletal muscle of streptozotocin (STZ)-induced diabetic rats and control rats. In the aortic rings of STZ rats, the Na-K-A TPase-dependent Rb-86/K uptake was reduced to 60.0 +/- 5.5% of the control value (P< 0.01). However, Na-K-ATPase activity in soleus skeletal muscle fi bers of STZ rats and paired control rats was similar, showing that the redu ction of Na-K-ATPase activity in aortas of STZ rats is tissue specific. To functionally distinguish the contributions of ouabain-resistant (<alpha>(1) ) and ouabain-sensitive (alpha (2) and alpha (3)) isoforms to the Na-K-ATPa se activity in aortic rings, we used either a high (10(-3) M) or a low (10( -5) M) ouabain concentration during Rb-86/K uptake. We found that the reduc tion in total Na-K-ATPase activity resulted from a dramatic decrement in ou abain-sensitive mediated Rb-86/K uptake (26.0 +/- 3.9% of control, P< 0.01) . Western blot analysis of membrane fractions from aortas of STZ rats demon strated a significant reduction in protein levels of <alpha>(1)- and alpha (2)-catalytic isoforms (alpha (1) = 71.3 +/- 9.8% of control values, P< 0.0 5; <alpha>(2) = 44.5 +/- 11.3% of control, P<0.01). In contrast, aortic rin gs from the STZ rats demonstrated an increase in NKCC1 activity (172.5 +/- 9.5%, P< 0.01); however, in heart tissue no difference in NKCC1 activity wa s seen between control and diabetic animals. Transport studies of endotheli um-denuded or intact aortic rings demonstrated that the endothelium stimula tes both Na- K-ATPase and Na- K-2Cl dependent Rb-86/K uptake. The endotheli um-dependent stimulation of Na-K-ATPase and Na-K-2Cl was not hampered by di abetes. We conclude that abnormal vascular vessel tone and function, report ed in STZ-induced diabetic rats, may be related to ion transport abnormalit ies caused by changes in Na- K-ATPase and Na- K-2Cl activities.