Impaired arteriolar mechanotransduction in experimental diabetes mellitus.
Decreased arteriolar distensibility in diabetes may impair signal transduction mechanisms that are required for converting a pressure stimulus into smooth muscle contraction. These studies aimed to determine if pressure-induced increases in arteriolar intracellular Ca(2+) are altered in diabetes and whether diabetes is associated with alterations in composition of the extracellular matrix. Studies of mechanical properties used single, isolated, and cannulated cremaster arterioles from streptozotocin (60 mg/kg) diabetic rats and age-matched controls. To measure Ca(2+)(i), arterioles were loaded with Fura 2 (5 microM) after which preparations were examined by fluorescence microscopy and image analysis. Matrix protein (type IV collagen, laminin, fibronectin) deposition was studied by immunohistochemistry. Over a range of 30-120 mm Hg control vessels showed a linear relationship (r = 0.98, p < 0.01) between intraluminal pressure and Ca(2+)(i). Vessels from diabetic 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 slope of the wall tension-Ca(2+)(i) relationship was significantly decreased in vessels from diabetic animals. These differences were ameliorated by treatment of diabetic animals (n = 5) with aminoguanidine. Increased content of type IV collagen, laminin and fibronectin in vessel media was evident after 2 weeks of diabetes and showed a further increase with duration of diabetes. The data suggest that for a given increase in luminal pressure arterioles from diabetic animals response with an attenuated rise in smooth muscle Ca(2+)(i). This mechanotransduction defect may relate to alterations in the composition of the extracellular matrix within the arteriolar wall.
Yu
G
G
Department of Physiology, Eastern Virginia Medical School, Norfolk, VA, USA.
Zou
H
H
Prewitt
R L
RL
Hill
M A
MA
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005353:Fibronectins / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D007797:Laminin / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015398:Signal Transduction / Q000502:physiology*
D005353:Fibronectins; D006146:Guanidines; D007797:Laminin; D003094:Collagen; C004479:pimagedine; D002118:Calcium