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 microg/min) and BK (62.5 ng/min and 4 microg/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.
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 microg/min) and BK (62.5 ng/min and 4 microg/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.
Authors: T Heare; N J Alp; D A Priestman; A B Kulkarni; P Qasba; T D Butters; R A Dwek; K Clarke; K M Channon; F M Platt Journal: J Inherit Metab Dis Date: 2006-12-25 Impact factor: 4.982
Authors: Miroslaw Janczura; Grazyna Bochenek; Roman Nowobilski; Jerzy Dropinski; Katarzyna Kotula-Horowitz; Bartosz Laskowicz; Andrzej Stanisz; Jacek Lelakowski; Teresa Domagala Journal: PLoS One Date: 2015-08-14 Impact factor: 3.240