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Cardiovascular-Kidney Interactions in Health and Disease

Hemoglobin, NO, and 20-HETE interactions in mediating cerebral vasoconstriction following SAH

¹Department of Physiology, ²Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin; and ³Medicinal Research Laboratories, Taisho Pharmaceutical Company, Saitama, Japan

Submitted 24 June 2005 ; accepted in final form 6 September 2005

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-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 µM) 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.

subarachnoid hemorrhage; nitric oxide; 20-hydroxyeicosatetraenoic acid

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