Changes in vagal activity and response to muscarinic receptor agonists with age

The response to vagal nerve and muscarinic receptor stimulation was evaluated in young (90 day), adult (365 day) and old (730 day) male F-344 rats anesthetized with urethane. Bilateral vagotomy produced a significant increase in heart rate in the young and adult animals (p < 0.05), while no change in heart rate occurred in the old animals. Stimulation of the right vagus nerve produced a frequency dependent decrease in response to right vagus nerve stimulation with age (p < 0.05; analysis of variance), i.e., old animals had a smaller decrease in heart rate over the same frequency range of nerve stimulation than either the young or adult animals. The effect of age on the response of the muscarinic receptor was examined using cumulative doses of methacholine administered by bolus injection. Methacholine produced a dose dependent decrease in heart rate and blood pressure. The heart rate response to methacholine was diminished in the older animals (p < 0.05; analysis of variance). Similar results were obtained after atropine although the doses of methacholine employed were much greater. In contrast, although methacholine decreased blood pressure in all animals at each age there was no change in the hypotensive response to methacholine with age. These data indicate that there is a diminution in vagal control of heart rate with age as well as the response of the vagus nerve to stimulation. Furthermore, the response of the muscarinic receptor in the heart declines with age while that in the peripheral vasculature does not.