Hypoglycemia selectively abolishes hypoxic reactivity of pial arterioles in piglets: role of adenosine.
Episodes of hypoxia often occur in hypoglycemic newborns, but it is not known whether dysfunctions in cerebrovascular regulation contribute to brain injury incurred by these affected neonates. We tested the hypotheses that 1) perinatal hypoglycemia impairs cerebrovascular responses to hypoxia and 2) a reduced vascular smooth muscle sensitivity to adenosine accounts for this impairment. Responses of 25- to 50-mu m-diam pial arterioles were determined using the cranial window technique in isoflurane-anesthetized newborn piglets < 5 days of age. Hypoxia (arterial PO2 = 28 +/- 1 mmHg) caused a 47 +/- 5% increase (P = 0.0008) in arteriolar diameter, 89% of which could be blocked by prior superfusion of the window space with the preferential A2-adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX; 50 microM). Insulin-induced hypoglycemia (blood glucose = 18 +/- 1 mg/dl without isoelectric electroencephalogram) caused a 31 +/- 5% increase (P = 0.002) in arteriolar diameter; however, no additional dilatative response to hypoxia (arterial PO2 = 28 +/- 1 mmHg) could be elicited in these animals. Arteriolar dilation of 41 +/- 6% (P = 0.002) induced by superfusion of 20 microM adenosine under normoglycemic conditions was also completely abolished after the animals were rendered hypoglycemic. Unlike the response to hypoxia and adenosine, hypoglycemia only attenuated prostanoid-dependent dilations to hypercapnia (arterial PCO2 = 68 +/- 3 mmHg) by 55 +/- 9%. These results indicate that, in the newborn, hypoglycemia selectively abolishes hypoxic reactivity through an impairment in adenosine-mediated cerebrovascular dilation.
Park
T S
TS
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri 63110.
Gonzales
E R
ER
Shah
A R
AR
Gidday
J M
JM
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics; D006935:Hypercapnia / Q000503:physiopathology; D007003:Hypoglycemia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D010841:Pia Mater / Q000098:blood supply*; D058915:Purinergic P1 Receptor Antagonists; D013552:Swine; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation
D058915:Purinergic P1 Receptor Antagonists; C057837:3,7-dimethyl-1-propargylxanthine; D000241:Adenosine; D013805:Theobromine