Role of nitric oxide and endothelium in rat pial vessel dilation response to isoflurane.
Isoflurane induces cerebral hyperemia. We sought to assess whether isoflurane induces cerebral microvessel dilation in vivo, and if so, to determine whether nitric oxide (NO) and endothelium are involved. By using a rat closed cranial window model, pial arterioles and venules of 30-70 microns in diameter were measured using intravital microscopy. The cerebral microvascular dilatory response was recorded as percent change of diameter from baseline. The pial vessels were suffused with sodium nitroprusside (SNP) or S-nitroso-acetyl-penicillamine (SNAP) to verify intact vascular smooth muscle relaxation function, and with adenosine diphosphate (ADP) and/or acetylcholine (ACh) to verify endothelial NO-generating capability. To isolate NO's role in the cerebral microvascular effects of isoflurane (Protocol I), microvessels were studied with and without nitric oxide synthase (NOS) inhibition by topically applied nitro-L-arginine methyl ester (L-NAME). In controls, L-NAME was replaced by its inactive enantiomer, nitro-D-arginine methyl ester (D-NAME). Mercury light plus fluorescein dye (LD) endothelial injury (Protocol II) was used to delineate an endothelium-mediated mechanism. Subsequently, vasodilator applications were repeated to verify the desired effects of the interventions and followed by suffusion of isoflurane 1%, 2%, and 3% (Protocol I) or isoflurane 3% (Protocol II). Suffusions of SNP, ADP, and ACh induced diameter increases of 15%-30%. NOS inhibition with L-NAME greatly attenuated ADP and ACh responses, but did not alter the SNP response, confirming that NO generation was blocked, but not NO action. These responses were unaffected in D-NAME-suffused rats. Isoflurane dilated arterioles 17% and venules 6% in the presence of D-NAME suffusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Anesthesiology, University of Illinois at Chicago.
H M
HM
Koenig
D A
DA
Pelligrino
Q
Q
Wang
R F
RF
Albrecht
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D014664:Vasodilation / Q000187:drug effects*
D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D007530:Isoflurane; D010396:Penicillamine; D000109:Acetylcholine