Absence of histamine-induced nitric oxide release in the human radial artery: implications for vasospasm of coronary artery bypass vessels

1 Cardiovascular Research, Physiology Institute and Center for Integrative Human Physiology, University of Zürich, and Department of Cardiology, Cardiovascular Center, University Hospital, Zürich; 2 Cardiovascular Research, Department of Clinical Research, University of Bern and Clinic for Cardiovascular Surgery, University Hospital, Bern; 3 Clinic for Cardiovascular Surgery, Cardiovascular Center, University Hospital, Zürich; and 4 Dermatology, University Hospital, Zürich, Switzerland Submitted 22 March 2005 ; accepted in final form 12 October 2005 Radial artery (RA) bypass grafts can develop severe vasospasm. As histamine is known to induce vasospasm, its effect on RA was assessed compared with 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, N -nitro- L -arginine methyl ester ( L -NAME), or the H 2 -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 H 2 -receptor in RA than MA or SV. Western blots revealed similar endothelial nitric oxide (NO) synthase expression in all three vessels. Relaxations to acetylcholine were identical in RA and MA. Thus histamine releases NO by activating the endothelial H 2 -receptor, the expression of which is much lower in RA than MA or SV. H 2 -receptor activation also releases prostaglandins in SV, partially antagonizing NO. The lack of histamine-induced NO production represents a possible mechanism of RA vasospasm. endothelium-dependent relaxation; heterogeneity; receptor Address for reprint requests and other correspondence: F. C. Tanner, Cardiovascular Research, Physiology Institute, Univ. of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland (e-mail: felix.tanner{at}access.unizh.ch )