Role of calcium in adrenergic neurochemical transmission in the aging heart.
The effect of modification of extracellular Ca2+ concentration ([Ca2+]0), the administration of the neuronal Ca2+ channel blocker, omega-conotoxin, and the calcium (Ca2+) ionophore, ionomycin, were examined in the isolated heart of male Fisher-344 rats 6 and 24 months of age. Hearts with the right cardiac sympathetic nerve intact were isolated and perfused with Krebs-Ringer solution containing cocaine (10(-6) M) to block uptake 1, metanephrine (10(-6) M) to block uptake 2 and yohimbine (3 X 10(-6) M) to prevent alpha 2 receptor inhibition of Ca2+ influx. The nerve was stimulated with frequencies of 2, 6 and 12 Hz for 1 min and NE output was determined by high-performance liquid chromatography/electrochemical methods. Effluent of hearts from 6-month-old rats contained higher levels of NE than effluent of hearts from 24-month-old rats at all frequencies of stimulation when perfused with either normal (1.2 mM), low (0.3 mM) or high (4.8 mM) [Ca2+]0. Even when high [Ca2+]0 was used to make more Ca2+ available, the amount of NE in the effluent of 24-month-old animal hearts was only approximately 54% of that found in the effluent of 6-month-old animal hearts perfused with normal [Ca2+]0. omega-Conotoxin caused a greater decrease in NE release in the older preparations suggesting that the neuronal Ca2+ channels of older preparations are more susceptible to blockade than those of younger preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
Roberts
J
J
Medical College of Pennsylvania/Eastern Pennsylvania Psychiatric Institute, Department of Pharmacology, Philadelphia.
Mortimer
M L
ML
Ryan
P J
PJ
Johnson
M D
MD
Tumer
N
N
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000494:pharmacology*; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D015759:Ionomycin; D002118:Calcium; D009638:Norepinephrine