Protamine induces vasorelaxation of human internal thoracic artery by endothelial NO-synthase pathway.
BACKGROUND
Protamine is commonly used in cardiac surgery to reverse the anticoagulant effects of heparin. We investigated the role of different nitric oxide synthase pathways in the response of the human internal thoracic artery to protamine and evaluated whether heparin could prevent this effect.


METHODS
A tension-recording method was used to obtain baseline measurements of contractions of human internal thoracic artery rings achieved with norepinephrine. Isolated internal thoracic artery rings were suspended in two organ chambers. One contained Krebs-Henseleit solution and served as control. The other contained a heparin or Nomega-Nitro-L-arginine (L-NAM, an inhibitor of both endothelial and inducible nitric oxide synthase) or a specific inhibitor of inducible nitric oxide synthase, aminoguanidine. Increasing doses of protamine were added to both chambers and dose-response curves were obtained.


RESULTS
Protamine was found to relax contracted internal thoracic arteries 56% +/- 4.7% of baseline measurements in a concentration-dependent manner. When L-NAM was added, protamine caused only a slight decrease of tension. There were no differences in the relaxing effect of protamine in the presence of aminoguanidine or heparin.


CONCLUSIONS
Protamine induces nitric oxide-dependent relaxation of the internal thoracic artery by activation of endothelial nitric oxide synthase pathway. Heparin could not prevent this relaxing effect of protamine.
Pevni
D
D
Department of Thoracic and Cardiovascular Surgery, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Israel.
Gurevich
J
J
Frolkis
I
I
Keren
G
G
Shapira
I
I
Paz
J
J
Kramer
A
A
Locker
C
C
Mohr
R
R
D001026:Coronary Artery Bypass; D003326:Coronary Circulation / Q000187:drug effects*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011479:Protamines / Q000494:pharmacology*; D013895:Thoracic Arteries / Q000187:drug effects / Q000637:transplantation; D014664:Vasodilation / Q000187:drug effects*
D011479:Protamines; D019001:Nitric Oxide Synthase