Fosinopril Improves Regulation of Vascular Tone in Mesenteric Bed of Diabetic Rats

Publisher Website
Google Scholar
Abstract
Because diabetes mellitus leads to vascular dysfunction, we examined the microvascular endothelial and smooth muscle function in long-term diabetes and a possible influence of fosinopril treatment (10 mg/kg). We investigated isolated perfused mesenteric beds of diabetic rats (4 groups: control, control + fosinopril, diabetes, diabetes + fosinopril; diabetes of 6-month duration, induced by streptozotocin, STC) were investigated using computer-assisted microvideoangiometry. Vascular diameter of four different vascular regions [classified as conductive (G1, 303 +/- 6.5 mu m and G2, 239 +/- 6.3 mu m) and resistance (G3, 192 +/- 4.5 mu m and G4, 124 +/- 2.6 mu m) vessel generations; resting conditions, control group] were increased in diabetes by approximately 20%. However, the endothelium-dependent relaxation in response to 1 mu M acetylcholine (ACh) was reduced from 38-44% to 20-25% (diabetes mellitus) with maximal impairment in G4 vessels. This could be significantly antagonized by fosinopril treatment. Similarly, vasodilation in response to 1 mu M glyceroltrinitrate (GTN) was reduced from 50-58 to 20-30%, but was partially prevented by fosinopril (32-38%), whereas potassium chloride (KCl)-induced vasoconstriction did not show differences between the groups. Inhibition of nitric oxide (NO) synthesis by 3 mu M L-NG-nitro arginine (L-NNA) resulted in a slight vasoconstriction of all vessels (12-25%), with maximum response in G3/G4. This was not altered by disease or treatment. We conclude that (a) long-term diabetes leads to endothelial and smooth muscle dysfunction with reduced capability of vasodilation and either an impairment of NO release or a reduced smooth muscle responsiveness to and (b) a predominant impairment of NO-dependent regulation in small resistance vessels, and (c) that fosinopril treatment can at least partially prevent this vascular dysfunction.