Changes in vascular responses of the basilar artery to acetylcholine and endothelin-1 in an experimental rabbit vasospasm model

Summary

¶Background. This study aimed to clarify the characteristics of the basilar arteries of rabbits two and seven days after subarachnoid haemorrhage (SAH) and to investigate the influence of hypoxia on vascular responses to acetylcholine and endothelin-1.

Methods. Thirty four New Zealand white rabbits were divided into 3 groups: 1) control (n=6), 2) 2 days post SAH (n=15), and 3) 7 days post SAH (n=13). Rabbits in the groups 2 and 3 underwent vertebral angiography before sacrifice. Harvested vascular rings were suspended in a small vessel myograph system for isometric tension recording in response to vasodilatory and vasoconstrictory stimulation in oxygenated (95% O₂/5% CO₂) and hypoxic (95% N₂/5% CO₂) conditions. To investigate the response to a vasodilator, acetylcholine (ACh) (10⁻⁷ to 3×10⁻⁴ M) was applied to a basilar artery pre-contracted with histamine (10⁻⁶∼10⁻⁵ M). To investigate the response to a vasoconstrictor, the effect of endothelin-1 (ET-1) (10⁻¹¹ to 3×10⁻⁸ M) was observed in quiescent rings.

Findings. Seven of 15 rabbits that underwent angiography two days after operation showed vasospasm to 64.3±11.2% of the original diameter; likewise seven of the 13 rabbits studied seven days after operation showed vasospasm to 64.9±10.9% of the original diameter. Hypoxic conditions significantly reduced the relaxation response to ACh but did not influence basilar artery contraction to ET-1. Responses to ACh and ET-1 did not differ significantly in vessels from animals with or without vasospasm at 2 days. In contrast, at 7 days vascular responses to ACh and ET-1 were significantly less in vessels from animals with vasospasm than those without (p=0.029, 0.032), and also less than in vessels from animals with vasospasm at day 2 (p=0.002, 0.004). There was not a significant difference in the vascular responses of basilar arteries from animals without vasospasm.

Interpretation. The markedly lower vascular responses of basilar arteries of rabbits to ACh and ET-1 found seven days after SAH may relate to delayed vasospasm in patients with SAH.