Effect of age on presynaptic beta2 receptor mediated responses in the rat heart.
Presynaptic alpha2 adrenergic receptor inhibition of norepinephrine (NE) release is diminished in older animals [1]. To determine whether presynaptic beta2 adrenergic receptor facilitation of NE release is also affected by age, the effect of propranolol on neurally-induced NE release was examined in perfused heart preparations isolated from 6- and 24-month-old rats. The heart was isolated with the right cardiac sympathetic nerve and then was stimulated electrically in the absence and presence of propranolol (10(-8)-10(-6) M). NE content in the effluent was measured by an HPLC/EC methodology. The data indicate that there is a greater suppression of NE release by propranolol in preparation isolated from younger animals. For example, in nerve-heart preparations of 6-month-old animals stimulated at 12 Hz, propranolol (10(-6) M) reduced the amount of NE released by 34% whereas in preparations from 24-month-old animals at 12 Hz there was no significant change in the NE overflow. Like the alpha2 receptor mechanism, autoregulation of NE release by presynaptic beta2 receptors is diminished in older animals. Lack of presynaptic autoregulation may explain in part, the reduced capacity of adrenergic influences to control and regulate cardiac function in older animals.
Mortimer
M L
ML
Medical College of Pennsylvania, Eastern Pennsylvania Psychiatric Institute, Department of Pharmacology, Philadelphia 19129.
Tumer
N
N
Johnson
M D
MD
Roberts
J
J
D000375:Aging / Q000502:physiology*; D000818:Animals; D006321:Heart / Q000502:physiology*; D006706:Homeostasis; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D009638:Norepinephrine