Noradrenaline-induced changes in intracellular Ca2+ and tension in mesenteric arteries from diabetic rats

1 The purpose of this investigation was to determine whether enhanced contr actile responses to noradrenaline (NA) of mesenteric arteries from rats wit h chronic streptozotocin-induced diabetes are associated with increases in mean cytosolic [Ca2+](i). 2 [Ca2+](i) was measured with fura 2-AM, and was monitored simultaneously w ith tension in perfused endothelium-denuded mesenteric arterial rings from 12-14 week diabetic rats and age- and gender-matched control rats. 3 Basal [Ca2+](i) (expressed as R-n, the normalized fura 2 ratio) was not s ignificantly different in arteries from control and diabetic rats. Similarl y, no differences between control and diabetic arteries in the tension or [ Ca2+](i) responses to 80 mm KCI in the presence of phentolamine were detect ed. 4 The rate of tension development, peak tension and integrated tension in r esponse to 30 muM NA were all significantly greater in diabetic than contro l arteries. However, this was not associated with enhancement of the corres ponding [Ca2+](i) responses in the diabetic arteries. 5 Peak contractile responses to perfusion with both 0.3 and 3 muM NA, but p eak [Ca2+](i) only in response to 0.3 pm NA, were significantly greater in diabetic than control arteries. 6 NA (30 muM) produced a greater increase in both peak tension and [Ca2+](i ) in diabetic than control arteries perfused with Ca2+-free solution contai ning 1 mM EGTA. Neither the rate nor the magnitude of NA-induced Ca2+ influ x appeared to be altered in the diabetic arteries. 7 The enhanced sustained contractile response of diabetic arteries to NA ap pears to be dissociated from increases in [Ca2+](i), and may be due to othe r factors, such as an increase in the Ca2+ sensitivity of the contractile p roteins.