Abstract
Endothelial dysfunction is a main feature of type 2 diabetes. Impairment in vascular smooth muscle cell function may also contribute to diabetes‐associated microvascular and macrovascular complications. We hypothesized that mesenteric resistance arteries (MA) from non‐obese rats with type 2 diabetes (Goto‐Kakizaki, GK) would have reduced responses to soluble guanylyl cyclase (sGC) activation as compared to controls (Wistar). Endothelium‐dependent and –independent relaxation was assessed in isolated arterial segments mounted in a wire myograph. GK MA had reduced responses to acetylcholine (ACh; ‐logEC50: 7.92 ± 0.08 vs. 7.65 ± 0.06, p<0.05) and sodium nitroprusside (SNP; ‐logEC50: 8.43 ± 0.08 vs. 7.84 ± 0.06, p<0.05), but there were no group differences in 8‐Br‐cGMP‐induced relaxation and PKG‐1 and phosphorylated VASPSer239 expression (p>0.05). GK MA had attenuated responses to BAY41‐2272 (heme‐dependent sGC stimulator; ‐logEC50: 7.55 ± 0.07 vs. 6.88 ± 0.08, p<0.05) and BAY58‐2667 (heme‐independent sGC stimulator; ‐logEC50: 10.82 ± 0.07 vs. 10.27 ± 0.08, p<0.05) compared to control values but pharmacological inhibition of sGC abolished these differences. A reduction in sGC activity may account for impaired vascular smooth muscle responsiveness to dilatory stimuli in type 2 diabetes.
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