Hemoglobin, NO, and 20-HETE interactions in mediating cerebral vasoconstriction following SAH. Am J Physiol Regul Integr Comp Physiol 2006 Jan;290(1):R84-9
Date
09/17/2005Pubmed ID
16166205DOI
10.1152/ajpregu.00445.2005Scopus ID
2-s2.0-33644833670 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
Recent studies have indicated that 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to the fall in cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH), but the factors that stimulate the production of 20-HETE are unknown. This study examines the role of vasoactive factors released by clotting blood vs. the scavenging of nitric oxide (NO) by hemoglobin (Hb) in the fall in CBF after SAH. Intracisternal (icv) injection of blood produced a greater and more prolonged (120 vs. 30 min) decrease in CBF than that produced by a 4% solution of Hb. Pretreating rats with N(omega)-nitro-l-arginine methyl ester (l-NAME; 10 mg/kg iv) to block the synthesis of NO had no effect on the fall in CBF produced by an icv injection of blood. l-NAME enhanced rather than attenuated the fall in CBF produced by an icv injection of Hb. Blockade of the synthesis of 20-HETE with TS-011 (0.1 mg/kg iv) prevented the sustained fall in CBF produced by an icv injection of blood and the transient vasoconstrictor response to Hb. Hb (0.1%) reduced the diameter of the basilar artery (BA) of rats in vitro by 10 +/- 2%. This response was reversed by TS-011 (100 nM). Pretreatment of vessels with l-NAME (300 muM) reduced the diameter of BA and blocked the subsequent vasoconstrictor response to the addition of Hb to the bath. TS-011 returned the diameter of vessels exposed to l-NAME and Hb to that of control. These results suggest that the fall in CBF after SAH is largely due to the release of vasoactive factors by clotting blood rather than the scavenging of NO by Hb and that 20-HETE contributes the vasoconstrictor response of cerebral vessels to both Hb and blood.
Author List
Takeuchi K, Miyata N, Renic M, Harder DR, Roman RJMESH terms used to index this publication - Major topics in bold
AnimalsBrain
Cerebrovascular Circulation
Formamides
Hemoglobins
Hydroxyeicosatetraenoic Acids
Male
Morpholines
NG-Nitroarginine Methyl Ester
Nitric Oxide
Rats
Rats, Sprague-Dawley
Subarachnoid Hemorrhage
Time Factors
Vasoconstriction
