Myogenic tone and reactivity of cerebral arteries in type II diabetic BBZDR/Wor rat.
BBZDR/Wor rat is a new model of type II diabetes with spontaneous obesity and clinical characteristics close to human diabetes. In this study the time-course of cerebroarterial dysfunction was characterized. Posterior cerebral arteries from BBZDR/Wor rats and their age-matched lean controls were pressurized to 70 mm Hg in an arteriograph. Effects of intraluminal pressure and different pharmacological agents on myogenic tone were evaluated. Pressure-myogenic tone curves in diabetic arteries were similar to that in non-diabetic arteries at pre-diabetic age, showed leftward shift at 4 weeks and were significantly different with higher myogenic tone at 5 and 8 months of diabetes. Age-dependent decrease in myogenic tone was observed in non-diabetic arteries. Dilation to histamine was similar to that in non-diabetic arteries at pre-diabetic and at 4 weeks but significantly reduced at 5 and 8 months of diabetes. Bradykinin-mediated dilation was significantly reduced in early and chronic diabetes, whereas (+/-)-S-nitroso-N-acetylpenicillamine (SNAP)-mediated dilation was decreased modestly at 8 months of diabetes. Sensitivity and constriction to 5-hydroxytryptamine were increased in early and chronic diabetes. Responses to bradykinin and 5-hydroxytryptamine were decreased and increased, respectively. Myogenic tone was significantly less sensitive to (lower pIC(50)) U-73122 than normal arteries at 4 weeks and 8 months of diabetes suggesting an increased activation of phospholipase C (PLC). This study shows that pressure-mediated autoregulation of cerebral arteries in type II diabetes operates at higher resistance. Endothelium-dependent dilation was decreased with chronic diabetes with increased sensitivity to constrictor agonist. Endothelium-independent dilation was modestly affected. Arterial hyper-reactivity to pressure and constrictor agonist were likely due to increased PLC activation.
Jarajapu
Yagna P R
YP
Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610-0267, USA. yjarajap@wfubmc.edu
Guberski
Dennis L
DL
Grant
Maria B
MB
Knot
Harm J
HJ
D000367:Age Factors; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D008297:Male; D020769:Posterior Cerebral Artery / Q000503:physiopathology*; D051381:Rats; D011913:Rats, Inbred BB; D011924:Rats, Zucker; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
D012701:Serotonin; D026423:S-Nitroso-N-Acetylpenicillamine; D010738:Type C Phospholipases; D001920:Bradykinin