Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans

Abhiram Prasad, Syed Husain, William Schenke, Rita Mincemoyer, Neal Epstein, Arshed A. Quyyumi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

OBJECTIVES: The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors. BACKGROUND: Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone. METHODS: In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 μg/min) and BK (62.5 ng/min and 4 μg/min), and endothelium-independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin-converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed. RESULTS: There was progressive impairment in ACH-mediated microvascular dilation with increasing numbers of risk factors (p = 0.025, analysis of variance). By contrast, BK- and sodium nitroprusside-mediated microvascular dilation was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK; segments that constricted or dilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constricted with pacing. Finally, epicardial BK responses were depressed in patients with high ACE levels and in those with the ACE DD genotype. CONCLUSIONS: Endothelial dysfunction in atherosclerosis appears to be receptor-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteries during physiologic stress is better represented by BK and not by ACH responses. Bradykinin activity and, hence, physiologic coronary vasomotion appears to be influenced by serum ACE levels and the ACE insertion/deletion genotype. (C) 2000 by the American College of Cardiology.

Original languageEnglish (US)
Pages (from-to)1467-1473
Number of pages7
JournalJournal of the American College of Cardiology
Volume36
Issue number5
DOIs
StatePublished - Nov 1 2000
Externally publishedYes

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Bradykinin Receptors
Bradykinin
Peptidyl-Dipeptidase A
Acetylcholine
Atherosclerosis
Kinins
Genotype
Nitroprusside
Endothelium
Blood Vessels
Dilatation
Muscarinic Receptors
Serum
Vasodilation
Coronary Vessels
Analysis of Variance

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans. / Prasad, Abhiram; Husain, Syed; Schenke, William; Mincemoyer, Rita; Epstein, Neal; Quyyumi, Arshed A.

In: Journal of the American College of Cardiology, Vol. 36, No. 5, 01.11.2000, p. 1467-1473.

Research output: Contribution to journalArticle

Prasad, Abhiram ; Husain, Syed ; Schenke, William ; Mincemoyer, Rita ; Epstein, Neal ; Quyyumi, Arshed A. / Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans. In: Journal of the American College of Cardiology. 2000 ; Vol. 36, No. 5. pp. 1467-1473.
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abstract = "OBJECTIVES: The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors. BACKGROUND: Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone. METHODS: In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 μg/min) and BK (62.5 ng/min and 4 μg/min), and endothelium-independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin-converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed. RESULTS: There was progressive impairment in ACH-mediated microvascular dilation with increasing numbers of risk factors (p = 0.025, analysis of variance). By contrast, BK- and sodium nitroprusside-mediated microvascular dilation was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK; segments that constricted or dilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constricted with pacing. Finally, epicardial BK responses were depressed in patients with high ACE levels and in those with the ACE DD genotype. CONCLUSIONS: Endothelial dysfunction in atherosclerosis appears to be receptor-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteries during physiologic stress is better represented by BK and not by ACH responses. Bradykinin activity and, hence, physiologic coronary vasomotion appears to be influenced by serum ACE levels and the ACE insertion/deletion genotype. (C) 2000 by the American College of Cardiology.",
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AU - Husain, Syed

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AU - Epstein, Neal

AU - Quyyumi, Arshed A.

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N2 - OBJECTIVES: The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors. BACKGROUND: Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone. METHODS: In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 μg/min) and BK (62.5 ng/min and 4 μg/min), and endothelium-independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin-converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed. RESULTS: There was progressive impairment in ACH-mediated microvascular dilation with increasing numbers of risk factors (p = 0.025, analysis of variance). By contrast, BK- and sodium nitroprusside-mediated microvascular dilation was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK; segments that constricted or dilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constricted with pacing. Finally, epicardial BK responses were depressed in patients with high ACE levels and in those with the ACE DD genotype. CONCLUSIONS: Endothelial dysfunction in atherosclerosis appears to be receptor-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteries during physiologic stress is better represented by BK and not by ACH responses. Bradykinin activity and, hence, physiologic coronary vasomotion appears to be influenced by serum ACE levels and the ACE insertion/deletion genotype. (C) 2000 by the American College of Cardiology.

AB - OBJECTIVES: The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors. BACKGROUND: Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone. METHODS: In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 μg/min) and BK (62.5 ng/min and 4 μg/min), and endothelium-independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin-converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed. RESULTS: There was progressive impairment in ACH-mediated microvascular dilation with increasing numbers of risk factors (p = 0.025, analysis of variance). By contrast, BK- and sodium nitroprusside-mediated microvascular dilation was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK; segments that constricted or dilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constricted with pacing. Finally, epicardial BK responses were depressed in patients with high ACE levels and in those with the ACE DD genotype. CONCLUSIONS: Endothelial dysfunction in atherosclerosis appears to be receptor-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteries during physiologic stress is better represented by BK and not by ACH responses. Bradykinin activity and, hence, physiologic coronary vasomotion appears to be influenced by serum ACE levels and the ACE insertion/deletion genotype. (C) 2000 by the American College of Cardiology.

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