Noradrenaline‐induced changes in intracellular Ca 2+ and tension in mesenteric arteries from diabetic rats

The purpose of this investigation was to determine whether enhanced contractile responses to noradrenaline (NA) of mesenteric arteries from rats with chronic streptozotocin‐induced diabetes are associated with increases in mean cytosolic [Ca 2+ ] i . [Ca 2+ ] i was measured with fura 2‐AM, and was monitored simultaneously with tension in perfused endothelium‐denuded mesenteric arterial rings from 12 – 14 week diabetic rats and age‐ and gender‐matched control rats. Basal [Ca 2+ ] i (expressed as R n , the normalized fura 2 ratio) was not significantly different in arteries from control and diabetic rats. Similarly, no differences between control and diabetic arteries in the tension or [Ca 2+ ] i responses to 80 m M KCl in the presence of phentolamine were detected. The rate of tension development, peak tension and integrated tension in response to 30 μ M NA were all significantly greater in diabetic than control arteries. However, this was not associated with enhancement of the corresponding [Ca 2+ ] i responses in the diabetic arteries. Peak contractile responses to perfusion with both 0.3 and 3 μ M NA, but peak [Ca 2+ ] i only in response to 0.3 μ M NA, were significantly greater in diabetic than control arteries. NA (30 μ M ) produced a greater increase in both peak tension and [Ca 2+ ] i in diabetic than control arteries perfused with Ca 2+ ‐free solution containing 1 m M EGTA. Neither the rate nor the magnitude of NA‐induced Ca 2+ influx appeared to be altered in the diabetic arteries. The enhanced sustained contractile response of diabetic arteries to NA appears to be dissociated from increases in [Ca 2+ ] i , and may be due to other factors, such as an increase in the Ca 2+ sensitivity of the contractile proteins.British Journal of Pharmacology (2001) 134 , 179–187; doi: 10.1038/sj.bjp.0704221