Ageing is associated with increased 5-HT2-receptor affinity and decreased receptor reserve in rat isolated coronary...

1. The 5-hydroxytryptamine (5-HT)-receptor subtype and affinity for 5-HT was determined in large and small coronary arteries isolated as ring segments from the proximal and distal part of the left coronary artery of 3 month (young) and 2-year old (old) rats. 2. Ketanserin induced a rightward shift of the 5-HT concentration-response curve in both proximal and distal coronary arteries from young rats. The slopes of the Schild-plots were indistinguishable from unity and the estimated pA2 values were 9.11 and 9.27 for proximal and distal coronary arteries, respectively. These data indicate a homogeneous population of 5-HT2-like receptors in the coronary arteries. 3. The contractile effect of 5-HT as well as the sensitivity to 5-HT was greater in proximal and distal coronary arteries from old than from young rats. 4. The apparent 5-HT2-receptor affinity, -log(KA[M]), and fractional receptor-occupancy for relative responses between 10% and 90% of maximum was determined by partial irreversible inhibition of the 5-HT2-receptors with phenoxybenzamine. 5. Ageing was associated with an increase in 5-HT2-receptor affinity for 5-HT in both proximal and distal coronary arteries, whereas the fractional receptor occupancy for half-maximal response to 5-HT decreased with age. 6. 5-HT2-receptor affinity for 5-HT could account for the 5-HT sensitivity of distal coronary arteries in both young and old rats but not in proximal coronary arteries as the slope of the regression line of plots of 5-HT2-receptor affinity vs. sensitivity was indistinguishable from unity in only the distal vessels. 7. The 5-HT2-receptor affinity for 5-HT was linearly correlated to the fractional receptor occupancy for half maximal response, suggesting that the 5-HT2-receptor reserve or density down-regulates the receptor affinity for 5-HT. 8. The results indicate that the increase in 5-HT sensitivity and contractile effect in rat coronary arteries rely upon an increase in both 5-HT2-receptor agonist affinity and efficiency of the excitation-contraction coupling process in the vascular smooth muscle.