Different effects of protamine on canine coronary microvessel and conductance arteries: evidence of hyperpolarizing factor release.
Protamine administration may lead to systemic hypotension, perhaps because of vasodilatation produced by endothelial nitric oxide. This study compared release of vasoactive substances from canine coronary microvessels with that from paired conductance arteries.



Microvessels were mounted in a videoscopic no-flow system, and circumflex arteries were studied in organ chambers; both were induced to contract by endothelin-1.



Protamine (10 to 160 micrograms/mL) produced concentration-dependent relaxation in both microvessel and conductance arteries (46% +/- 14% maximal relaxations in microvessel and 82% +/- 15% in conductance arteries, n = 10 each). Removal of the endothelium abolished this relaxation (P < .05, n = 6). Indomethacin (10(-5) mol/L) did not alter the relaxation in either group (51% +/- 10% in microvessel and 103% +/- 7% in conductance arteries, n = 6 each). NG-monomethyl-L-arginine (L-NMMA, 10(-4) mol/L) attenuated relaxation in conductance arteries (38% +/- 12%, P = .04, n = 6) but had no effect on microvessel arteries (58% +/- 10%, n = 6). Tetraethylammonium chloride (10(-3) mol/L), an inhibitor of voltage-dependent potassium channels, had no effect on conductance arteries (103% +/- 9%, n = 6) but abolished relaxation in microvessels (-25% +/- 11%, P = .03, n = 6).



Protamine sulfate causes endothelium-dependent relaxation in microvessel and conductance arteries in the heart by different mechanisms--that is, by nitric oxide release in conductance arteries and by endothelium-derived hyperpolarizing factor (EDHF) release in microvessels. This is the first description of the release of EDHF in response to protamine administration.
Cable
D G
DG
Section of Cardiovascular Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Sorajja
P
P
Oeltjen
M R
MR
Schaff
H V
HV
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D001685:Biological Factors / Q000096:biosynthesis / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis; D006494:Heparin Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D011479:Protamines / Q000494:pharmacology*; D014664:Vasodilation / Q000502:physiology
D001685:Biological Factors; D006494:Heparin Antagonists; D011479:Protamines; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D011464:Epoprostenol