Impairment of endothelium-dependent dilatation of the basilar artery during diabetes mellitus.
The goal of this study was to determine whether responses of the basilar artery are altered during diabetes mellitus. We measured the diameter of the basilar artery in vivo in non-diabetic and diabetic rats (streptozotocin; 50-60 mg/kg i.p.). Responses of the basilar artery to agonists, which presumably produce dilatation by releasing endothelium-derived relaxing factor (EDRF), were impaired in diabetic rats compared to non-diabetic rats. Acetylcholine (1.0 and 10 microM) dilated the basilar artery by 13 +/- 2 and 26 +/- 4% (means +/- S.E.M.), respectively, in non-diabetic rats, but by only 4 +/- 1 and 9 +/- 2%, respectively, in diabetic rats (P less than 0.05). Bradykinin (1.0 and 10 microM) dilated the basilar artery by 14 +/- 2 and 35 +/- 6% (means +/- S.E.M.), respectively, in non-diabetic rats, but by only 5 +/- 1 and 6 +/- 2%, respectively, in diabetic rats (P less than 0.05). The response to nitroglycerin was similar in non-diabetic and diabetic rats. Thus, impairment of vasodilatation in diabetic rats in response to acetylcholine and bradykinin is not related to non-specific impaired of vasodilatation. Next, we examined the possibility that impaired dilator responses of the basilar artery in response to acetylcholine and bradykinin in diabetic rats may be related to the activation of the thromboxane A2-prostaglandin H2 receptor. SQ 29548 (a specific thromboxane A2-prostaglandin H2 receptor antagonist) did not alter responses of the basilar artery to acetylcholine and bradykinin. These findings suggest that diabetes mellitus impairs endothelium-dependent dilatation of the basilar artery.(ABSTRACT TRUNCATED AT 250 WORDS)
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology*; D001920:Bradykinin / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D051381:Rats; D011982:Receptors, Prostaglandin / Q000502:physiology*; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; C045749:SQ 29548; D000109:Acetylcholine; D001920:Bradykinin