Pharmacologic activation of the human coronary microcirculation in vitro

Endothelium-dependent dilation and differential responses to acetylcholine

Francis J. Miller, Kevin C Dellsperger, David D. Gutterman

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Objectives: In vivo studies of the human coronary resistance circulation cannot control for indirect effects of myocardial metabolism, compression, and neurohumoral influences. This study directly examined the vasodilator responses of the human coronary microcirculation to both receptor-dependent and -independent agonists. Methods: Atrial arterioles were dissected from human right atrial appendage (103 ± 2 μm diameter, n = 185 vessels from 145 patients) obtained at the time of cardiopulmonary bypass and left ventricular vessels from explanted human hearts (148 ± 10 μm diameter, n = 57 vessels from 18 patients). After dissection, vessels were mounted onto pipettes in Kreb's buffer under conditions of zero flow and at a constant distending pressure of 60 mmHg. Drugs were applied extraluminally and steady state changes in diameter measured with videomicroscopy. Results: After contraction by endothelin or spontaneous tone, increasing concentrations of adenosine diphosphate (ADP) produced a similar dose-dependent dilation in vessels from atria (maximum 89 ± 4%, n = 76) and ventricles (maximum 74 ± 9%, n = 10). The dilation to ADP was abolished by mechanical removal of the endothelium. Similar dilator responses were found to bradykinin, substance P, arachidonic acid, and the calcium ionophore A23187 in both atria and ventricle. In contrast, acetylcholine (ACh) constricted all atrial vessels (-58 ± 3%, n = 63) regardless of patient age or underlying disease. This constriction was attenuated by denudation, but not affected by inhibition of nitric oxide synthase or cyclo-oxygenase. Microvessels isolated from human ventricle exhibited a heterogeneous response to ACh with dilation being the predominant response. Conclusions: We conclude that isolated human coronary arterioles demonstrate endothelium-dependent dilation. However, the response to acetylcholine is unique with vasoconstriction in atrial vessels and dilation in ventricular arterioles.

Original languageEnglish (US)
Pages (from-to)744-750
Number of pages7
JournalCardiovascular Research
Volume38
Issue number3
DOIs
StatePublished - Jun 1 1998

Fingerprint

Microcirculation
Acetylcholine
Endothelium
Dilatation
Arterioles
Adenosine Diphosphate
Atrial Appendage
Video Microscopy
Coronary Circulation
Calcium Ionophores
Endothelins
Calcimycin
Bradykinin
Prostaglandin-Endoperoxide Synthases
Substance P
Microvessels
Vasoconstriction
Cardiopulmonary Bypass
Vasodilator Agents
Arachidonic Acid

Keywords

  • Acetylcholine
  • Adenosine diphosphate
  • Atria
  • Coronary circulation
  • Human
  • Microcirculation
  • Nitric oxide
  • Ventricle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Pharmacologic activation of the human coronary microcirculation in vitro : Endothelium-dependent dilation and differential responses to acetylcholine. / Miller, Francis J.; Dellsperger, Kevin C; Gutterman, David D.

In: Cardiovascular Research, Vol. 38, No. 3, 01.06.1998, p. 744-750.

Research output: Contribution to journalArticle

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abstract = "Objectives: In vivo studies of the human coronary resistance circulation cannot control for indirect effects of myocardial metabolism, compression, and neurohumoral influences. This study directly examined the vasodilator responses of the human coronary microcirculation to both receptor-dependent and -independent agonists. Methods: Atrial arterioles were dissected from human right atrial appendage (103 ± 2 μm diameter, n = 185 vessels from 145 patients) obtained at the time of cardiopulmonary bypass and left ventricular vessels from explanted human hearts (148 ± 10 μm diameter, n = 57 vessels from 18 patients). After dissection, vessels were mounted onto pipettes in Kreb's buffer under conditions of zero flow and at a constant distending pressure of 60 mmHg. Drugs were applied extraluminally and steady state changes in diameter measured with videomicroscopy. Results: After contraction by endothelin or spontaneous tone, increasing concentrations of adenosine diphosphate (ADP) produced a similar dose-dependent dilation in vessels from atria (maximum 89 ± 4{\%}, n = 76) and ventricles (maximum 74 ± 9{\%}, n = 10). The dilation to ADP was abolished by mechanical removal of the endothelium. Similar dilator responses were found to bradykinin, substance P, arachidonic acid, and the calcium ionophore A23187 in both atria and ventricle. In contrast, acetylcholine (ACh) constricted all atrial vessels (-58 ± 3{\%}, n = 63) regardless of patient age or underlying disease. This constriction was attenuated by denudation, but not affected by inhibition of nitric oxide synthase or cyclo-oxygenase. Microvessels isolated from human ventricle exhibited a heterogeneous response to ACh with dilation being the predominant response. Conclusions: We conclude that isolated human coronary arterioles demonstrate endothelium-dependent dilation. However, the response to acetylcholine is unique with vasoconstriction in atrial vessels and dilation in ventricular arterioles.",
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