Impaired cerebrovascular reactivity after cortical spreading depression in rats: Restoration by nitric oxide or cGMP.
We investigated the role of the NO/cGMP system in the vasodilatory response to hypercapnia after cortical spreading depression (CSD) in barbiturate anesthetized rats in vivo. Regional cerebral blood flow (rCBF) was measured by laser Doppler flowmetry (LDF). Hypercapnia (arterial pCO2 50-60 mm Hg) increased rCBF by 2.8+/-1.0%/mm Hg (n = 34). Fifteen minutes after CSD, resting rCBF was reduced to 87%, and rCBF response to hypercapnia was abolished (p < 0.001, n = 28). Within 1 h after CSD, only little restoration of vascular reactivity occurred. Topical application of the NO-donors S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine (SIN1), or spermine/NO complex (Sperm/NO), or of the cell permeable guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-Br-cGMP reestablished resting rCBF to values measured before CSD, and reversed CSD-induced attenuation of the cerebrovascular response to hypercapnia. Restoration of resting rCBF to pre-CSD level by the NO-independent vasodilator papaverine had no effect on the attenuated hypercapnic response. In conclusion, we have shown that the compromised vascular reactivity to hypercapnia after CSD can be reversed to normal reactivity by restoration of the basal NO or cGMP concentration in the cortex, suggesting a reduction of the cerebrovascular NO or cGMP concentration following CSD.
Scheckenbach
Klaus Ernst Ludwig
KE
Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, 10098 Berlin, Germany.
Dreier
Jens P
JP
Dirnagl
Ulrich
U
Lindauer
Ute
U
D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D006935:Hypercapnia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism* / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000627:therapeutic use; D010396:Penicillamine / Q000031:analogs & derivatives / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000627:therapeutic use; D013873:Thionucleotides / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D013873:Thionucleotides; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; D013096:Spermine; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D010396:Penicillamine; D006152:Cyclic GMP