Differential H1- and H2-receptor-mediated histamine responses of canine epicardial conductance and distal resistance coronary vessels

W. L. Miller, A. A. Bove

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The contributions of histamine (H1 or H2) receptor-mediated responses and, therefore, the effects of histamine blocking agents are unclear with regard to regulation of proximal epicardial and distal resistance coronary arteries. This study was designed to evaluate the effects of selective H1- and H2-receptor antagonists on epicardial and resistance vessels in the closed chest dog model. Histamine, diphenhydramine (H1 blocker), and cimetidine (H2 blocker) were infused into the left anterior descending coronary artery (LAD), and responses were studied by quantitative coronary angiography and flow measurements (133Xe washout). Histamine infusion alone produced a significant dilation of the proximal LAD (13% above control) only at the highest dose (45 μg/min), while LAD flow was increased by 128%. In the presence of H1 blocker, histamine produced significantly greater epicardial dilation (55% above control). The flow response curve was shifted to the right in the presence of H1 blocker, but the flow attenuation was overcome by the highest histamine dose. In contrast, the H2 blocker attenuated both epicardial dilation (6% below control) and flow response (31% above control) to the highest histamine dose. Results support a differential regulation of proximal epicardial and distal resistance vessels to histamine with epicardial arteries demonstrating H1-mediated vasoconstriction and H2-mediated vasodilation and distal resistance vessels showing H1- and H2-mediated vasodilation. In addition, these findings suggest that H1 blockade may antagonize histamine-related vasoconstriction and vasospasm, while H2 blockers may permit unopposed H1-mediated vasoconstriction of epicardial arteries and also limit resistance vessel vasodilatory responsiveness in the presence of elevated tissue histamine, as may occur in atherosclerotic coronary artery disease.

Original languageEnglish (US)
Pages (from-to)226-232
Number of pages7
JournalCirculation Research
Volume62
Issue number2
StatePublished - 1988

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Histamine H1 Receptors
Histamine H2 Receptors
Histamine
Canidae
Coronary Vessels
Vasoconstriction
Histamine H1 Antagonists
Dilatation
Vasodilation
Arteries
Histamine Agents
Diphenhydramine
Cimetidine
Coronary Angiography
Coronary Artery Disease
Thorax
Dogs

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Differential H1- and H2-receptor-mediated histamine responses of canine epicardial conductance and distal resistance coronary vessels. / Miller, W. L.; Bove, A. A.

In: Circulation Research, Vol. 62, No. 2, 1988, p. 226-232.

Research output: Contribution to journalArticle

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