NOREPINEPHRINE-MEDIATED CALCIUM SIGNALING IS ALTERED IN VASCULAR SMOOTH-MUSCLE OF DIABETIC RAT

We studied the influence of diabetes on norepinephrine (NE)-induced ch anges in intracellular free Ca2+ levels (receptor-mediated Ca2+ signal ing) in single tail artery vascular smooth muscle (VSM) cells. VSM cel ls from 12-16 week streptozotocin-induced diabetic (SID) rats showed a n increase in sensitivity to NE when compared to control VSM cells in that the concentration of NE needed to elicit half maximal response of the initial Ca2+ transient was reduced more than 4-fold though the ma ximal response attained was apparently reduced, In addition, the slope factor (steepness) of the dose-response relation was lowered 4-fold. Moreover, VSM cells of diabetic animals had a higher incidence of NE-i nduced Ca2+ oscillatory responses. The shift of the dose-response curv e to the left, coupled with a higher incidence of oscillations, indica te that the noradrenergic receptor-mediated Ca2+ signaling pathways in tail artery VSM of diabetic rat may be altered.