Insulin resistance does not impair contractile responses of cerebral arteries.
Insulin resistance (IR) impairs endothelium-mediated vasodilation in cerebral arteries as well as K+ channel function in vascular smooth muscle. Peripheral arteries also show an impaired endothelium-dependent vasodilation in IR and concomitantly show an enhanced contractile response to endothelin-1 (ET-1). However, the contractile responses of the cerebral arteries in IR have not been examined systematically. This study examined the contractile responses of pressurized isolated middle cerebral arteries (MCAs) in fructose-fed IR and control rats. IR MCAs showed no difference in pressure-mediated (80 mmHg) vasoconstriction compared to controls, either in time to develop spontaneous tone (control: 61+/-3 min, n=30; IR: 63+/-2 min, n=26) or in the degree of that tone (control: 60 min: 33+/-2%, n=22 vs. IR 60 min: 34+/-3%, n=17). MCAs treated with ET-1 (10(-8.5) M) constrict similarly in control (53+/-3%, n=14) and IR (53+/-3%, n=14) arteries. Constrictor responses to U46619 (10(-6) M) are also similar in control (48+/-9%, n=8) and IR (42+/-5%, n=6) MCAs as are responses to extraluminal uridine 5'-triphosphate (UTP; 10(-4.5) M) (control: 35+/-7%, n=11 vs. IR: 38+/-3%, n=10). These findings demonstrate that constrictor responses remain intact in IR despite a selective impairment of dilator responses and endothelial and vascular smooth muscle K+ channel function in cerebral arteries. Thus, it appears that the increased susceptibility to cerebrovascular abnormalities associated with IR and diabetes (including cerebral ischemia, stroke, vertebrobasilar transient ischemic attacks) is not due to an enhanced vasoreactivity to constrictor agents.
Simandle
Steve A
SA
Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, United States. ssimandl@wfubmc.edu
Erdös
Benedek
B
Snipes
James A
JA
Miller
Allison W
AW
Busija
David W
DW
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D002536:Cerebral Arteries / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism; D013997:Time Factors; D014544:Uridine Triphosphate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D017466:Receptors, Endothelin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D014544:Uridine Triphosphate