Altered microvascular reactivity in streptozotocin-induced diabetes in rats.
This study examined the effect of short-term streptozotocin-induced diabetes in rats on the response of cremaster muscle arterioles to angiotensin II (ANG II) and vasodilatory prostaglandins. Topically applied ANG II (10(-10) to 10(-6) M) caused significantly greater vasoconstriction of third-order arterioles in diabetic animals in comparison with controls. For example, in response to 10(-6) M ANG II arterioles of the diabetic animals constricted to 43 +/- 10% of basal diameter compared with controls' 67 +/- 6% (P less than 0.05). Furthermore, the magnitude of the secondary vasodilatation after ANG II-induced constriction was decreased in diabetic animals (108 +/- 4 and 131 +/- 9%, P less than 0.025). Cyclooxygenase inhibition resulted in marked arteriolar constriction, with this effect being less evident in diabetic animals. In response to indomethacin (2.8 x 10(-5) M), arterioles of the diabetic animals constricted to 84 +/- 7% of basal diameter compared with 56 +/- 4% in controls (P less than 0.01). Arterioles of the diabetic animals were less responsive to exogenous prostaglandin I2 (PGI2) and PGE2 (10(-12) to 10(-6) M) despite evidence of increased in vitro PGI2 production. The data demonstrate potentiation of the vasoconstrictor response and a diminution of the secondary vasodilator response to ANG II in experimental diabetes. These alterations may be due, in part, to decreased responsiveness of skeletal muscle arterioles to vasodilatory prostaglandins.
Hill
M A
MA
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Larkins
R G
RG
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000503:physiopathology*; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology*; D016861:Cyclooxygenase Inhibitors; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D000804:Angiotensin II; D013311:Streptozocin; D011464:Epoprostenol; D007213:Indomethacin