Chronic cystamine treatment inhibits small artery remodelling in rats.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Pharmacology, University of Aarhus, Aarhus, Denmark.
Ashkan
A
Eftekhari
Awahan
A
Rahman
Louise Holm
LH
Schaebel
Hua
H
Chen
Claus Vitrup
CV
Rasmussen
Christian
C
Aalkjaer
Carsten Leander
CL
Buus
Michael J
MJ
Mulvany
D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003538:Cystamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005782:Gels; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007260:Infusion Pumps; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018613:Microscopy, Confocal; D010656:Phenylephrine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D017208:Rats, Wistar; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D005782:Gels; D014662:Vasoconstrictor Agents; D017311:Amlodipine; D010656:Phenylephrine; D003094:Collagen; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D003538:Cystamine