Age- and endothelium-dependent changes in coronary artery reactivity to serotonin and calcium.
The influence of ageing and endothelium removal on the sensitivity and contractile response of rat coronary arteries to intracellular Ca2+ ([Ca2+]i) during activation with serotonin (5-HT) and membrane depolarisation with 125 mM K+ was investigated. The sensitivity and contractile response of coronary arteries to 5-HT were significantly higher in 2-year-old than in 3-month-old rats. The receptor responsible for the 5-HT-induced contractions in coronary arteries belongs to a population of 5-HT2 receptors in both young and old rats based on the Schild plot. The resting levels of [Ca2+]i and active tension were both increased by age and endothelium removal. During depolarisation with 125 mM K+, the sensitivity to [Ca2+]i and maximal tension induced by [Ca2+]i were not affected by age or endothelium. During activation with 10 microM 5-HT, the maximal tension induced by [Ca2+]i was increased by age but not affected by endothelium, whereas the sensitivity to [Ca2+]i was increased by endothelium removal. In conclusion, ageing is associated with an increased sensitivity to 5-HT in rat coronary small arteries. The increased sensitivity to 5-HT seems to involve an augmented contractile response to [Ca 2+]i in 5-HT-activated coronary arteries and a diminished endothelial basal vasodilator function.
Simonsen
Anja Hviid
AH
Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark.
Sheykhzade
Majid
M
Berg Nyborg
Niels C
NC
D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D012701:Serotonin; D002118:Calcium