Histaminergic receptors modulate the coronary vascular response in isolated guinea pig hearts. Role of nitric oxide |
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| Authors: | S Pierpaoli C Marzocca M G Bello W Schunack P F Mannaioni E Masini |
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| Institution: | (1) Department of Preclinical and Clinical Pharmacology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy;(2) Institute of Pharmacology, University of Berlin, Königin-Luise-Strasse 2–4, 14195 Berlin, Germany |
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| Abstract: | Objective: The effects of histamine and of histamine receptor agonists and antagonists on the coronary outflow and on the generation of nitric oxide (NO) were evaluated on isolated guinea pig hearts.Methods: Isolated guinea pig hearts were perfused for 50 min in a Langendorff apparatus with histamine (10–7– 10–8 M), in the absence or in the presence of NG-monome-thyl-L-arginine (L-NMMA, 10–4 M), a NO synthase inhibitor and of triprolidine (3 10–8 M) and cimetidine (10–7 M), H1 receptor and H2 receptor antagonists, and with trifluoromethyl-phenylhistamine (TFMPH, 10–7 M) and dimaprit (10–7 M), H1 and H2 receptor agonists. The effects of (R)- -methylhistamine (10–7 M), a H3 receptor agonist and of FUB 181 (10–7 M), a H3 receptor antagonist, were studied in the presence of bradykinin (10–7 M).Results: Histamine increases the coronary outflow and the generation of NO in a concentration-dependent fashion. The effects were completely abolished by blocking NO-synthase (NOS) with L-NMMA (10 –4 M). The effects were also abolished by cimetidine (10 –7 M), H 2 receptor antagonist, and only scarcely affected by triprolidine (310 –8 M), H 1 receptor antagonist. The effects were reproduced by dimaprit (10 –7 M), H 2 receptor agonist, and only scarcely by TFMPH (10 –7 M), a selective H 1 receptor agonist. Bradykinin (10 –7 M) produces a sustained coronary dilation paralleled by a marked increase in the generation of NO; the effects were significantly reduced by L-NMMA. The stimulation of H 3 receptors by (R)--methylhistamine (10 –7 M) significantly reduced both effects, which reverted to normal with FUB 181 (10 –7 M), an H 3 receptor antagonist.Conclusion: These results suggest that, in isolated guinea pig hearts, histamine produces coronary dilation through an H 2 /H 3 -dependent mechanism involving the generation of nitric oxide.Received 3 December 2002; returned for revision 8 April 2003; accepted by M. Parnham 26 May 2003 |
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| Keywords: | Guinea pig heart Histamine Bradykinin Nitric oxide Coronary dilation |
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