Influence of nitric oxide synthase and kinin antagonists on metabolic parameters in chronic streptozotocin-induced diabetes mellitus.
In vivo administration of HOE 140 (a new bradykinin receptor antagonist) and L-NAME (nitric oxide synthase inhibitor) was performed in chronic streptozotocin-diabetic rats. Basal increases (in umol.g dw-1) in liver (45.0 +/- 3.4.1) and uterine (40.0 +/- 2.95) triglyceride levels in diabetic animals vs control (liver: 34.0 +/- 3.87; uterus: 30.2 +/- 4.01) were partially prevented by L-NAME (p < 0.01), HOE 140 (p < 0.01) and L-NAME + HOE 140 (p < 0.01). High glycogen levels (in mg.g dw-1) observed in diabetic uterine tissue (3.07 +/- 0.90), and decreased glycogen content detected in diabetic liver (11.64 +/- 1.50) vs. control (uterus: 1.59 +/- 0.15, liver: 17.25 +/- 0.87) were unaffected. Uterine 14CO2 production from 14C-U-Glucose (in uCi.mg dw), which is lower in diabetic (35.0 +/- 5.12) than in control (50.12 +/- 4.54) tissues, was improved by HOE 140 (p < 0.05) and L-NAME+HOE 140 (p < 0.05), while hepatic glucose oxidation was not increased by the drugs. Glycemia levels were decreased in diabetic rats injected with L-NAME and L-NAME plus HOE 140. Pancreatic 6-Keto-prostaglandin F1 alpha to Thromboxane B2 ratio was lower in diabetic animals than in controls, and L-NAME and/or HOE 140 treatment prevented the decrement. These findings suggest that vasoactive compounds might prevent streptozotocin-induced damage in pancreatic tissue from chronic diabetic rats.
González
E
E
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Barcelona, España.
Roselló-Catafau
J
J
Xaus
C
C
Jawerbaum
A
A
Novaro
V
V
Gómez
G
G
Gelpí
E
E
Gimeno
M A
MA
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002245:Carbon Dioxide / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013929:Thromboxane B2 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D001786:Blood Glucose; D065168:Bradykinin Receptor Antagonists; D009566:Nitrates; D009573:Nitrites; D014280:Triglycerides; D002245:Carbon Dioxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C065679:icatibant; D006003:Glycogen; D019001:Nitric Oxide Synthase; D005947:Glucose; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester