title: Fosinopril improves regulation of vascular tone in mesenteric bed of diabetic rats.
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.
authors.affiliation: Institute for Pharmacology, University of Cologne, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Olbrich
authors.forename: P
authors.initials: P
authors.lastname: Rosen
authors.forename: R D
authors.initials: RD
authors.lastname: Hilgers
authors.forename: S
authors.initials: S
authors.lastname: Dhein
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000187:drug effects; D017328:Fosinopril / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D013311:Streptozocin; D017328:Fosinopril