Key result
Aging in rats was associated with a greater sensitivity to the cholinergic agonist carbachol for coronary vasoconstriction, but no difference in alpha adrenergic response.
Why the study?
Does aging alter coronary vascular responses to cholinergic and alpha adrenergic stimulation in isolated rat hearts?
Does aging alter coronary vascular responses to cholinergic and alpha adrenergic stimulation in isolated rat hearts?
Aging is associated with a striking enhancement of coronary vascular sensitivity to cholinergic, but not alpha-adrenergic, stimuli in a rat model, which may contribute to age-related coronary spasm.
Answers are grounded in this paper and cite their sources.
Preclinical age effects on coronary responses should not change practice; leaves open human translation and mechanisms.
OBJECTIVE: The aim was to determine whether aging alters coronary vascular responses to cholinergic and alpha adrenergic stimulation. METHODS: Changes in coronary perfusion pressure and myocardial contractility in response to infusion of cholinergic and alpha adrenergic agonists and antagonists were determined in isolated Langendorff perfused hearts from adult (6-8 months old) and aged (28-30 months old) Fischer 344 rats. RESULTS: In electrically paced hearts (250 beats.min-1), perfused at constant perfusate flow rate, the cholinergic agonist carbachol (10(-10)-10(6)M) elicited concentration dependent coronary vasoconstriction. The maximum response and the sensitivity to carbachol were more than twofold greater in the aged than in the adult heart: concentration of carbachol producing 50% increase in coronary perfusion pressure: adult 916(SEM 210) nM; aged 21(7) nM; p < 0.01. Under these experimental conditions, the negative inotropic response elicited by carbachol was also relatively greater (approximately twofold) in the aged hearts. A similar age related difference in coronary vascular response to carbachol was also observed in potassium (18 mM KCl) arrested, non-beating, constant flow perfused hearts. In adult and aged hearts, the carbachol induced vasoconstriction was mediated by vascular (M3) muscarinic receptors as judged from blockade of the response by the non-selective muscarinic receptor antagonist atropine, but not by the cardioselective (M2) muscarinic receptor antagonist AFDX-116. The Ca2+ channel antagonist verapamil markedly attenuated the carbachol induced coronary vasoconstriction, indicating that a large component of the contractile Ca2+ mobilised by vascular muscarinic receptor activation is derived via influx of extracellular Ca2+. The alpha adrenergic agonist phenylephrine (10(-10)-10(6)M) produced concentration dependent coronary vasoconstriction; there was no age related difference in this alpha adrenergic response. CONCLUSIONS: There is striking enhancement of coronary vascular response to cholinergic but not alpha adrenergic stimuli with aging. Such age related cholinergic hypersensitivity may contribute to the high incidence of coronary artery spasm and impairment of coronary blood flow, cardiac energy metabolism, and contractile function that occurs with aging.
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Su et al. (1993) studied Aging-related coronary vascular responses. Aging vs. Adult rats (6-8 months old) was evaluated on Concentration of carbachol producing 50% increase in coronary perfusion pressure (p=< 0.01). Aging in rats was associated with a greater sensitivity to the cholinergic agonist carbachol for coronary vasoconstriction, but no difference in alpha adrenergic response.
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