Submitted on March 22, 2005
Accepted on October 12, 2005
Absence of Histamine-Induced Nitric Oxide Release in the Human Radial Artery - Implications for Vasospasm of Coronary Artery Bypass Vessels
Barbara E Stahli1, Helen Greutert1, Shaoping Mei2, Philipp Graf2, Karin Frischknecht1, Mario Stalder3, Lars Englberger3, Andreas Kunzli4, Leo Scharer5, Thomas F Luscher6, Thierry P Carrel3, and Felix C Tanner6*
1 Physiology Institute, University of Zurich, Cardiovascular Research, Zurich, Switzerland; University of Zurich, Center for Integrative Human Physiology, Zurich, Switzerland
2 Department of Clinical Research, University of Bern, Cardiovascular Research, Bern, Switzerland
3 University Hospital, Clinic for Cardiovascular Surgery, Bern, Switzerland; Department of Clinical Research, University of Bern, Cardiovascular Research, Bern, Switzerland
4 University Hospital, Clinic for Cardiovascular Surgery, Cardiovascular Center, Zurich, Switzerland
5 University Hospital, Dermatology, Zurich, Switzerland
6 Physiology Institute, University of Zurich, Cardiovascular Research, Zurich, Switzerland; University of Zurich, Center for Integrative Human Physiology, Zurich, Switzerland; University Hospital, Department of Cardiology, Cardiovascular Center, Zurich, Switzerland
* To whom correspondence should be addressed. E-mail: felix.tanner{at}access.unizh.ch.
Radial artery (RA) bypass grafts can develop severe vasospasm. As histamine is known to induce vasospasm, its effect on RA was assessed in comparison to the classic bypass vessels internal mammary artery (MA) and saphenous vein (SV). The vessels were examined in organ chambers for isometric tension recording. Histamine induced contractions on baseline; the sensitivity was higher in RA and SV than MA. After precontraction with norepinephrine, histamine did not evoke relaxations of RA, but induced relaxations of MA and less of SV at lower concentrations; it induced contractions at higher concentrations reaching similar levels in all three vessels. Indomethacin did not affect the response of MA and RA, but potentiated relaxations and reduced contractions of SV. Endothelium removal, L-NAME, or the H2-receptor blocker cimetidine did not affect the response of RA, but inhibited relaxations and enhanced contractions in MA, and inhibited relaxations in SV; in the latter, only L-NAME enhanced contractions. Real-time PCR detected much lower expression of endothelial H2-receptor in RA than MA or SV. Western blots revealed similar endothelial NOS expression in all three vessels. Relaxations to acetylcholine were identical in RA and MA. Thus, histamine releases nitric oxide (NO) by activating the endothelial H2-receptor, whose expression is much lower in RA than MA or SV. H2-receptor activation also releases prostaglandins in SV, partially antagonizing NO. The lack of histamine-induced NO production represents a possible mechanism of RA vasospasm.
