Age related alteration in cholinergic but not alpha adrenergic response of rat coronary vasculature.
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.
Su
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Department of Physiology, University of Western Ontario, London, Canada.
Narayanan
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009924:Organ Culture Techniques; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011976:Receptors, Muscarinic / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D002217:Carbachol; D002118:Calcium