title: Chronic hyperglycemic diabetes in the rat is associated with a selective impairment of cerebral vasodilatory responses.
abstract: Diabetes has been reported to impair vasodilatory responses in the peripheral vascular tissue. However, little is known about vasodilatory function in the diabetic brain. We therefore studied, in the N2O-sedated, paralyzed, and artificially ventilated rat, the effects of chronic hyperglycemic diabetes on the cerebral blood flow (CBF) responses to 3 acutely imposed vasodilatory stimuli: hypoglycemia (HG) (plasma glucose = 1.6-1.9 mumol ml-1), hypoxia (HX) (PaO2 = 35-38 mm Hg), or hypercarbia HC) (PaCO2 = 75-78 mm Hg). In addition, we evaluated the somatosensory evoked potential (SSEP) and plasma catecholamine changes in rats exposed to acute glycemic reductions. Diabetes was induced via streptozotocin (STZ, 60 mg kg-1 i.p.). All results in diabetic rats were compared to those obtained in age-matched nondiabetic controls. The animals were studied at 6-8 weeks (HG experiments) or 4-6 months (HG, HX, and HC experiments) post-STZ. Values for CBF were obtained for the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) employing radiolabeled microspheres. Up to three CBF determinations were made in each animal. In 6-8 week diabetics vs. controls, CBF increased to a lesser value in the CX, SC, and BS (p less than 0.05). Thus, in the diabetics, going from chronic hyperglycemia to acute hypoglycemia, CBF values (in ml 100 g-1 min-1 +/- SD) increased (p less than 0.05) from 89 +/- 22 to 221 +/- 57 in the CX, from 82 +/- 21 to 160 +/- 52 in the SC, and from 79 +/- 34 to 237 +/- 125 in the BS. In controls, going from normoglycemia to acute hypoglycemia, the CBF changes (p less than 0.05) were 128 +/- 27 to 350 +/- 219 (CX), 117 +/- 11 to 358 +/- 206 (SC), and 130 +/- 29 to 452 +/- 254 (BS). CBF changes and absolute values in the CE were similar in the two groups. At 4-6 months post-STZ, a complete loss of the hypoglycemic CBF response was found in the CX, SC, and CE. In the BS, a CBF response to hypoglycemia was seen in the diabetic rats, with the CBF increasing from 114 +/- 28 (hyperglycemia) to 270 +/- 204 ml 100 g-1 min-1 (p less than 0.05), compared to a change from 147 +/- 36 (normoglycemia) to 455 +/- 299 ml 100 g-1 min-1 (p less than 0.05) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesiology, Michael Reese Hospital and Medical Center, Chicago, IL 60616.
authors.forename: D A
authors.initials: DA
authors.lastname: Pelligrino
authors.forename: R F
authors.initials: RF
authors.lastname: Albrecht
mesh_terms: D000818:Animals; D001769:Blood; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply*; D002560:Cerebrovascular Circulation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D005071:Evoked Potentials; D006863:Hydrogen-Ion Concentration; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010100:Oxygen / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation
chemical_list: D001786:Blood Glucose; D010100:Oxygen; D009638:Norepinephrine; D004837:Epinephrine