Impaired arteriolar mechanotransduction in experimental diabetes mellitus

Decreased arteriolar distensibility in diabetes may impair signal transduct ion mechanisms that are required for converting a pressure stimulus into sm ooth muscle contraction. These studies aimed to determine if pressure-induc ed increases in arteriolar intracellular Ca2+ (Ca2+) are altered in diabete s and whether diabetes is associated with alterations in composition of the extracellular matrix. Studies of mechanical properties used single, isolat ed, and cannulated cremaster arterioles from streptozotocin (60 mg/kg) diab etic rats and age-matched controls. To measure Ca-i(2+), arterioles were lo aded with Fura 2 (5 mu M) after which preparations were examined by fluores cence microscopy and image analysis. Matrix protein (type IV collagen, lami nin, fibronectin) deposition was studied by immunohistochemistry. Over a ra nge of 30-120 mm Hg control vessels showed a linear relationship (r = 0.98, p < 0.01) between intraluminal pressure and Ca-i(2+). Vessels from diabeti c animals also showed a linear relationship (r = 0.99, p < 0.01), however, the mean slope was significantly (p < 0.02) less in the diabetic (0.17 +/- 0.05, n = 5) compared to controls (0.51 +/- 0.09, n = 7). Similarly, the sl ope of the wall tension-Ca-i(2+) relationship was significantly decreased i n vessels from diabetic animals. These differences were ameliorated by trea tment of diabetic animals (n = 5) with aminoguanidine. Increased content of type IV collagen, laminin and fibronectin in vessel media was evident afte r 2 weeks of diabetes and showed a further increase with duration of diabet es. The data suggest that for a given increase in luminal pressure arteriol es from diabetic animals response with an attenuated rise in smooth muscle Ca-i(2+) This mechanotransduction defect may relate to alterations in the c omposition of the extracellular matrix within the arteriolar wall. (C) 2000 Elsevier Science Inc.