Persistence of the nitric oxide-dependent vasodilator pathway of cerebral vessels after experimental subarachnoid hemorrhage.

OBJECTIVE

Efficiency of the treatment of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) by interfering with the nitric oxide-cyclic guanosine monophospate (cGMP) pathway seems to be inconsistent. So far, it remains unclear whether or not insufficient access to the drugs or impaired reactivity of the vessels is responsible for this inconsistency. Therefore, the aim of the present investigation was to characterize this pathway on cerebral arteries during CVS.

METHODS

CVS was induced using the rat double hemorrhage model and was determined by magnetic resonance perfusion weighted imaging. Rats were sacrificed on Day 3 and Day 5 after SAH. Immunohistochemical staining of the basilar artery for endothelial nitric oxide synthases and the alpha- and beta-subunits of the soluble guanylate cyclase was performed. Basilar artery ring segments on Day 5 were used for measurement of isometric force. Concentration effect curves for acetylcholine, sodium nitroprusside, and 8-bromo-cGMP were constructed and compared by maximum effect and pD2.

RESULTS

The immunohistochemical expression of endothelial nitric oxide synthase was comparable in all groups. The soluble guanylate cyclase alpha- and beta-subunits were significantly diminished on Day 3, but recovered by Day 5. The relaxation attributable to acetylcholine and 8-bromo-cGMP was virtually identical in controls and during CVS. Relaxation attributable to sodium nitroprusside, however, was significantly enhanced after SAH (maximum effect, control: 88 +/- 12%; Day 5: 117 +/- 26%).

CONCLUSIONS

The present investigations suggest the persistence of endothelium-, nitric oxide-, and cGMP-dependent relaxation during CVS. Therefore, the treatment of CVS interfering with this pathway seems not to be limited by alterations inside the vessel wall.