Alpha 1 adrenergic receptor function in senescent Fischer 344 rat aorta.
There have been numerous conflicting reports concerning alpha 1 adrenergic receptor-mediated blood vessel contraction during aging and possible changes in alpha 1 receptor transduction mechanisms have not been investigated. These studies assess capacity of the aging vascular alpha 1 receptor to stimulate production of inositol phosphates, which are its intracellular second messengers, and to elicit a contractile response via this pathway. Aortic ring segments from mature adult (6 month old) and senescent (24 month old) Fischer 344 rats were incubated with [3H]myo-inositol and then stimulated with the alpha 1 agonist norepinephrine (NE, 10(-7)M-3 x 10(-5)M) in the presence of LiCl (10mM), an inhibitor of inositol phosphate metabolism. There was a substantial increase in inositol phosphate accumulation throughout the dose range in aortic rings from 24 month old rats compared to 6 month old rats. This is an alpha 1 receptor response since it is blocked by the alpha 1 antagonist prazosin but not by the alpha 2 antagonist yohimbine. Aortic inositol phosphate accumulation in response to serotonin did not change with age. To assess second messenger stimulated contraction, aortic ring segments were placed in Ca++ free buffer and then stimulated with NE. Under these conditions Ca++ influx is eliminated and contraction depends on the actions of intracellular second messengers. There is an age-related reduction in aortic contraction in Ca++ free buffer. These results suggest that aortic alpha 1 receptor-mediated formation of inositol phosphate intracellular second messengers is enhanced during aging. Despite this, the capacity of senescent arteries to elicit contraction utilizing second messenger pathways seems to be deficient.
Johnson
M D
MD
Department of Pharmacology, Medical College of Pennsylvania/EPPI, Philadelphia 19129.
Wray
A
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D012701:Serotonin; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin