Chronic Cystamine Treatment Inhibits Small Artery Remodelling in Rats

BACKGROUND/AIMS: We investigated whether the tissue transglutaminase inhibitor cystamine is able to inhibit remodelling of small arteries in vivo, a possibility suggested by recent in vitro experiments. METHODS: Using osmotic minipumps, phenylephrine, cystamine and/or amlodipine were infused for 1-2 weeks into 9-week-old Wistar rats. Small arteries were then removed for pressure myograph investigation. RESULTS: Phenylephrine infusion caused inward remodelling of the small arteries compared to vehicle infusion. The remodelling was abolished by concomitant infusion with cystamine; blood pressure was unaffected. Second, we investigated whether cystamine was able to inhibit outward remodelling. Rats were first infused with phenylephrine for 1 week, and some were infused for a further week with amlodipine with or without cystamine. Amlodipine caused 24% outward remodelling compared to vessels from rats at completion of the phenylephrine infusion. The outward remodelling was attenuated 86% by concomitant cystamine infusion. A series of in vitro experiments supported the inhibitory action of cystamine on tissue transglutaminase. CONCLUSION: The ability of cystamine to inhibit inward remodelling independent of blood pressure is consistent with a role of tissue transgluaminase in this process. It remains to be determined if the ability of cystamine to inhibit outward remodelling also involves inhibition of tissue transglutaminase.