Age-related alterations in cardiac parasympathetic responsiveness: a preliminary report

Baroreceptor control of the heart rate is reduced by ageing in animals and man. This has been ascribed to an age-related reduction in beta-adrenergic receptor density and cardiac responsiveness to sympathetic modulation. However, the baroreceptor-heart rate reflex largely depends on the vagus and the age-related changes in cardiac parasympathetic responsiveness have never been tested directly. We examined the heart rate responses to acetylcholine in six young (3-5 months) and six old (22-24 months) ketamine-anaesthetized, bilaterally vagotomized Sprague-Dawley rats instrumented with arterial and venous catheters. The acetylcholine was given as 2, 4 and 8 micrograms/kg intravenous bolus injections. Linear regressions between each dose of acetylcholine and the ensuing bradycardia were calculated. The acetylcholine-induced bradycardia was strikingly larger in old than in young rats, amounting to 20.9 +/- 4.4 and 8.6 +/- 1.5 beats/min per microgram per kg, respectively (P less than 0.05). Thus cardiac muscarinic receptor responsiveness is increased rather than reduced by ageing. Therefore not all functions involved in cardiovascular regulation show an age-related impairment, and some may even be enhanced as age progresses. It is also clear that mechanisms other than attenuation of cardiac responses to autonomic stimuli (central and/or afferent) account for the age-related impairment in the baroreceptor-heart rate reflex.