Vasoreactivity and prostacyclin release in streptozotocin-diabetic rats: effects of insulin or aldose reductase inhibition.
1. Alterations in vasoreactivity and endothelial cell function could underlie some of the vascular abnormalities in diabetes. To examine aspects of these phenomena we studied the effects of 4-6 weeks streptozotocin-induced diabetes in the rat on basal and angiotensin II (AII)-stimulated prostacyclin release from isolated lung, perfused at constant flow. In addition, pressure was monitored throughout the lung perfusion as an index of vasomotor tone. 2. The experiment also included lungs from groups of diabetic rats treated with either insulin or an aldose reductase inhibitor (imirestat), to determine whether these treatments influenced the development of any defects seen in untreated diabetes. 3. Despite some indication of a trend towards reduced prostacyclin release in lungs from diabetic rats, neither the basal nor AII-stimulated release was significantly different from that seen in tissues from control animals. There were no significant differences between groups in the average basal perfusion pressure and in either the absolute pressure response to AII or the time of this peak. 4. The area under the perfusion pressure curve during AII infusion was greater in lungs from diabetic animals than in controls indicating a prolonged vasoconstrictor response. This increased pressor response may indicate increased sensitivity of diabetic tissue to AII or a reduced production of vasodilators in response to the vasoconstriction. 5. Whichever mechanism was responsible, this alteration was prevented by insulin treatment but not by aldose reductase inhibition, implicating mechanisms probably unrelated to exaggerated polyol pathway flux.
Stevens
E J
EJ
William Harvey Research Institute, Department of Pharmacology, Queen Mary and Westfield College, University of London.
Willars
G B
GB
Lidbury
P
P
House
F
F
Tomlinson
D R
DR
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D050260:Carbohydrate Metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D011464:Epoprostenol / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D000804:Angiotensin II; D011464:Epoprostenol; D000449:Aldehyde Reductase