Effects of ischemia on cerebrovascular responses to N-methyl-D-aspartate in piglets.
We examined the effects of total global ischemia on cerebral arteriolar responses to N-methyl-D-aspartate (NMDA) in anesthetized newborn pigs. Arteriolar responses to 10(-4) M NMDA were determined before and after 10 to 20 min of ischemia caused by increasing intracranial pressure. Before ischemia, NMDA dilated arterioles by 30 +/- 5% (baseline = 88 +/- 2 microns; n = 6). However, after 10 min of ischemia, arteriolar dilation was reduced to 10 +/- 3% at 1 h (P < 0.05). At 2 and 4 h, NMDA-induced dilation was not different from preischemia values. Twenty minutes of ischemia had similar effects. Coadministration of 100 U/ml of superoxide dismutase did not restore arteriolar dilation to NMDA at 1 h after ischemia. Sodium nitroprusside dilated by 14 +/- 3 and 40 +/- 5% at 10(-6) and 10(-5) M before ischemia, respectively, and arteriolar responsiveness was not changed by ischemia (n = 6). Cortical nitric oxide synthase (NOS) activity, measured by the in vitro conversion of L-[14C]arginine to L-[14C]citrulline, was unaffected by ischemia (n = 12). We conclude that decreases in cerebral arteriolar responsiveness to NMDA are not due to impairment of NOS activity, enhanced degradation or chelation of nitric oxide (NO), or reduced vascular smooth muscle responsiveness to NO.
Busija
D W
DW
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem 27157, USA.
Meng
W
W
Bari
F
F
McGough
P S
PS
Errico
R A
RA
Tobin
J R
JR
Louis
T M
TM
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000201:enzymology; D002545:Brain Ischemia / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation
D009599:Nitroprusside; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase