Responsiveness, affinity constants and receptor reserves for serotonin on aortae of aged normotensive and hypertensive rats.
We have previously shown that the potency and affinity constants (K(A) values) for serotonin (5-HT) are greater, and the 5-HT2A-receptor reserve is lesser, on the aorta of 6-month-old spontaneously hypertensive rats (SHRs) compared with age-matched Wistar Kyoto normotensive (WKY) rats. The present study was undertaken to investigate whether these parameters are altered on the aorta with ageing and as hypertension progresses to heart failure. The effects of phenoxybenzamine on the serotonergic responses of the aortae of 24-month-old WKY rats and SHRs were determined. On WKY rat aorta, ageing from 6 to 24 months was associated with an increase in sensitivity and affinity for serotonin, and a loss of 5-HT2A-receptor reserve. On SHR aorta, ageing from 6 to 24 months was also associated with an increase in sensitivity and affinity for serotonin, but a loss of 5-HT2A-receptor reserve. The sensitivity to serotonin was greater on the 24-month-old SHR aorta (pD2 6.53) than age-matched WKY rat aorta (pD2 5.89). On the aorta of the 24-month-old WKY rats, the K(A) value for serotonin was 4.5 x 10(-6) M, and the receptor occupancies required for 20 and 50 % maximum responses were 12 and 29%, respectively. There was a similar affinity, but greater receptor reserves, for serotonin on the aorta of age-matched SHRs. In summary, we have shown changes in sensitivity, affinity and 5-HT2A-receptor reserves for serotonin on the aorta with ageing and in hypertension/heart failure.
Doggrell
S A
SA
Cardiovascular Pharmacology, Faculty of Medicine and Health Sciences, The University of Auckland, New Zealand. s_doggrell@yahoo.com
Chen
Y Y
YY
D000375:Aging / Q000502:physiology; D000465:Algorithms; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin