title: Mechanism of impaired responses of cerebral arterioles during diabetes mellitus.
abstract: The goal of this study was to determine the mechanism of impaired responses of cerebral arterioles during diabetes mellitus. To induce diabetes, rats were injected with streptozotocin. Rats were characterized as diabetic by a blood glucose of greater than 300 mg/dl. Diameter of pial arterioles was measured with intravital microscopy in nondiabetic and diabetic rats during superfusion with acetylcholine (ACh), ADP, the thromboxane (Tx) analogue U-46619, and nitroglycerin. ACh increased pial arteriolar diameter in nondiabetic rats and did not alter diameter in diameter in diabetic rats. ADP increased pial arteriolar diameter in nondiabetic rats and produced minimal changes in diameter of arterioles in diabetic rats. Tx analogue U-46619 produced similar constriction of cerebral arterioles in nondiabetic and diabetic rats. In addition, nitroglycerin produced similar dilatation of cerebral arterioles in nondiabetic and diabetic rats, suggesting that impaired dilatation of cerebral arterioles in diabetic rats was not related to nonspecific impairment of vasodilatation. Next, we examined the possibility that impaired responses of cerebral arterioles in diabetic rats in response to ACh and ADP may be related to production of a cyclooxygenase constrictor substance. Indomethacin and the TxA2-prostaglandin (PG) H2 receptor antagonist SQ 29548 restored dilator responses to ACh and ADP in diabetic rats toward that observed in nondiabetic rats. Indomethacin and SQ 29548 did not alter responses in nondiabetic rats. Thus diabetes mellitus impairs endothelium-dependent responses of cerebral arterioles. The mechanism of impaired responses of cerebral arterioles during diabetes mellitus appears to be related to the production of a cyclooxygenase constrictor substance and presumably related to stimulation of the TxA2-PGH2 receptor.
authors.affiliation: Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198.
authors.forename: W G
authors.initials: WG
authors.lastname: Mayhan
authors.forename: L K
authors.initials: LK
authors.lastname: Simmons
authors.forename: G M
authors.initials: GM
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000098:blood supply* / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011463:Prostaglandins H / Q000378:metabolism; D051381:Rats; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013931:Thromboxanes / Q000378:metabolism; D014661:Vasoconstriction; D014664:Vasodilation; D019323:omega-N-Methylarginine
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013931:Thromboxanes; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C045749:SQ 29548; D001120:Arginine; D007213:Indomethacin