Role of endothelium and nitric oxide in histamine-induced responses in human cranial arteries and detection of mRNA encoding H1- and H2-receptors by RT-PCR
Version of Record online: 3 FEB 2009
1997 British Pharmacological Society
British Journal of Pharmacology
Volume 121, Issue 1, pages 41–48, May 1997
How to Cite
Jansen-Olesen, I., Ottosson, A., Cantera, L., Strunk, S., Hjorth Lassen, L., Olesen, J., Mortensen, A., Engel, U. and Edvinsson, L. (1997), Role of endothelium and nitric oxide in histamine-induced responses in human cranial arteries and detection of mRNA encoding H1- and H2-receptors by RT-PCR. British Journal of Pharmacology, 121: 41–48. doi: 10.1038/sj.bjp.0701097
- Issue online: 3 FEB 2009
- Version of Record online: 3 FEB 2009
- (Received December 19, 1996, Accepted January 27, 1997)
- Histamine receptors;
- human cranial arteries;
- vasomotor responses;
- nitric oxide;
- vascular smooth muscle
Histamine induces relaxation of human cranial arteries. Studies have revealed that the relaxant histamine H1-receptor predominates in human cerebral and the H2-receptor in temporal arteries, while H1- and H2-receptors are of equal importance in the middle meningeal artery. The purpose of the present study was to examine the role of the endothelium and nitric oxide in histamine-induced responses and to show the presence of mRNA encoding H1- and H2-receptors in human cranial arteries.
Electrophoresis of polymerase chain reaction (PCR) products from human cerebral, middle meningeal and temporal arteries, demonstrated products corresponding to mRNA encoding both H1- and H2-receptors in arteries with and without endothelium. The amplified PCR products were sequenced and showed 100% homology with the published sequences of these histamine receptors.
A sensitive in vitro system was used to study vasomotor responses to histamine. In precontracted cerebral, middle meningeal and temporal arteries with and without endothelium, histamine caused a concentration-dependent relaxation with Imax values between 87% and 81% and pIC50 values between 8.14 and 7.15. In arteries without endothelium the histamine-induced relaxation was significantly less potent (Imax values between 87% and 66% and pIC50 values between 7.01 and 6.67) than in cranial arteries with an intact endothelium.
The addition of histamine to arteries without endothelium and pretreated with the histamine H2-antagonist, cimetidine (10−5M), caused a concentration-dependent contraction of the cranial arteries with Emax values between 86% and 29% and pEC50 values between 7.53 and 6.77. This contraction was blocked by the histamine H1-receptor antagonist, mepyramine (10−7M), and even turned into a relaxation with Imax values between 84% and 14% and pIC50 values between 7.42 and 5.86.
The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 3×10−5M) significantly inhibited the relaxant response to histamine in cerebral and temporal arteries (pIC50 values between 7.43 and 7.13). The combined treatment with L-NAME (3×10−5M) and cimetidine (10−5M) caused a further displacement of the concentration-response curve (pIC50 values between 7.14 and 6.57) and decreased the maximum relaxant responses in all three cranial arteries (Imax values between 62% and 39%).
In conclusion, this is the first study which show mRNA encoding histamine H1- and H2-receptors in human cranial arteries. The results indicate that histamine-induced relaxation of human cranial arteries is partially mediated via an endothelial H1-receptor coupled to the production of nitric oxide and partially via a H2-receptor associated with the smooth muscle cells. In addition, there is evidence for a contractile H1-receptor in the smooth muscle cells in these arteries.
British Journal of Pharmacology (1997) 121, 41–48; doi:10.1038/sj.bjp.0701097