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Mechanisms of histamine-induced coronary vasodilatation: H1-receptor-mediated release of endothelium-derived nitric oxide

Mechanisms of histamine-induced coronary vasodilatation: H1-receptor-mediated release of endothelium-derived nitric oxide
Mechanisms of histamine-induced coronary vasodilatation: H1-receptor-mediated release of endothelium-derived nitric oxide
Although the content of histamine in myocardial tissue is high, its contribution to the regulation of coronary blood flow has not been clearly defined. The aim of the present study was to investigate whether or not nitric oxide (NO), an important modulator of coronary vascular tone, is involved in histamine-induced coronary vasomotion and to characterize which histaminergic receptor subtype mediates this process. Isolated, constant-flow-perfused guinea pig hearts were challenged with histamine, the H1-receptor agonist pyridylethylamine (PYR) and the H2-receptor agonist dimaprit (DIM). Apart from coronary perfusion pressure (CPP), left ventricular pressure (LVP) and the development of contractile force (dp/dt), the release of NO and cyclic GMP (cGMP) were continuously measured. Histamine and DIM induced concentration dependently a coronary vasodilatation with an almost 50% decrease in CPP paralleled by an enhancement of LVP and dp/dt by more than 80%. PYR selectively reduced CPP by 47% without affecting LVP and dp/dt. Histamine- and PYR-induced coronary vasodilatation were paralleled by a more-than-twofold increase in basal cGMP release from isolated hearts, whereas DIM exerted no effects on cGMP release. Oxyhemoglobin (4 microM), an effective scavenger of NO, shifted the concentration-response curve for histamine- and PYR-induced changes in CPP significantly to the right and in parallel inhibited the increase in cGMP release. Histamine and PYR rapidly (within 2 s) decreased CPP, while the onset of DIM-induced coronary vasodilatation followed changes in LVP with a lag period of 10 s. Histamine increased basal NO release concentration dependently by a maximum of 351 +/- 21 pmol/min.
histamine, endothelium, nitric oxide, cGMP, coronary circulation
1018-1172
132-138
Kelm, Malte
db2bb062-32d7-4b50-9f65-8ba89ffa5f42
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Krebber, Thomas
7114f31f-154e-4bd0-ac27-b1439acb1f8b
Motz, Wolfgang
1f23e8c8-e0b2-478b-bbbc-5b84be6f87d4
Strauer, Bodo E.
7343fe67-ccf3-4079-94a0-ea6238979951
Kelm, Malte
db2bb062-32d7-4b50-9f65-8ba89ffa5f42
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Krebber, Thomas
7114f31f-154e-4bd0-ac27-b1439acb1f8b
Motz, Wolfgang
1f23e8c8-e0b2-478b-bbbc-5b84be6f87d4
Strauer, Bodo E.
7343fe67-ccf3-4079-94a0-ea6238979951

Kelm, Malte, Feelisch, Martin, Krebber, Thomas, Motz, Wolfgang and Strauer, Bodo E. (1993) Mechanisms of histamine-induced coronary vasodilatation: H1-receptor-mediated release of endothelium-derived nitric oxide. Journal of Vascular Research, 30 (3), 132-138. (doi:10.1159/000158987). (PMID:8518330)

Record type: Article

Abstract

Although the content of histamine in myocardial tissue is high, its contribution to the regulation of coronary blood flow has not been clearly defined. The aim of the present study was to investigate whether or not nitric oxide (NO), an important modulator of coronary vascular tone, is involved in histamine-induced coronary vasomotion and to characterize which histaminergic receptor subtype mediates this process. Isolated, constant-flow-perfused guinea pig hearts were challenged with histamine, the H1-receptor agonist pyridylethylamine (PYR) and the H2-receptor agonist dimaprit (DIM). Apart from coronary perfusion pressure (CPP), left ventricular pressure (LVP) and the development of contractile force (dp/dt), the release of NO and cyclic GMP (cGMP) were continuously measured. Histamine and DIM induced concentration dependently a coronary vasodilatation with an almost 50% decrease in CPP paralleled by an enhancement of LVP and dp/dt by more than 80%. PYR selectively reduced CPP by 47% without affecting LVP and dp/dt. Histamine- and PYR-induced coronary vasodilatation were paralleled by a more-than-twofold increase in basal cGMP release from isolated hearts, whereas DIM exerted no effects on cGMP release. Oxyhemoglobin (4 microM), an effective scavenger of NO, shifted the concentration-response curve for histamine- and PYR-induced changes in CPP significantly to the right and in parallel inhibited the increase in cGMP release. Histamine and PYR rapidly (within 2 s) decreased CPP, while the onset of DIM-induced coronary vasodilatation followed changes in LVP with a lag period of 10 s. Histamine increased basal NO release concentration dependently by a maximum of 351 +/- 21 pmol/min.

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Published date: May 1993
Keywords: histamine, endothelium, nitric oxide, cGMP, coronary circulation
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 337911
URI: https://eprints.soton.ac.uk/id/eprint/337911
ISSN: 1018-1172
PURE UUID: 6de4156a-17e2-463d-8126-e1bc94d2d417
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 30 May 2012 09:43
Last modified: 06 Jun 2018 12:29

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Author: Malte Kelm
Author: Martin Feelisch ORCID iD
Author: Thomas Krebber
Author: Wolfgang Motz
Author: Bodo E. Strauer

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