FOSINOPRIL IMPROVES REGULATION OF VASCULAR TONE IN MESENTERIC BED OF DIABETIC RATS

Because diabetes mellitus leads to vascular dysfunction, we examined t he microvascular endothelial and smooth muscle function in long-term d iabetes and a possible influence of fosinopril treatment (10 mg/kg). W e investigated isolated perfused mesenteric beds of diabetic rats (4 g roups: control, control + fosinopril, diabetes, diabetes + fosinopril; diabetes of 6-month duration, induced by streptozotocin, STC) were in vestigated using computer-assisted microvideoangiometry. Vascular diam eter 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 condi tions, control group] were increased in diabetes by similar to 20%. Ho wever, the endothelium-dependent relaxation in response to 1 mu M acet ylcholine (ACh) was reduced from 38-44% to 20-25% (diabetes mellitus) with maximal impairment in G4 vessels, This could be significantly ant agonized by fosinopril treatment. Similarly, vasodilation in response to 1 mu M glyceroltrinitrate (GTN) was reduced from 50-58 to 20-30%, b ut was partially prevented by fosinopril (32-38%), whereas potassium c hloride (KCl)-induced vasoconstriction did not show differences betwee n the groups. Inhibition of nitric oxide (NO) synthesis by 3 mu M L-N- G-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 lead s to endothelial and smooth muscle dysfunction with reduced capability of vasodilation and either an impairment of NO release or a reduced s mooth muscle responsiveness to and (b) a predominant impairment of NO- dependent regulation in small resistance vessels, and (c) that fosinop ril treatment can at least partially prevent this vascular dysfunction .