SEROTONINERGIC RECEPTOR SUBTYPE IN CORONARY-ARTERY SMOOTH-MUSCLE FROMYOUNG AND ATHEROSCLEROTIC RABBIT

In rabbits fed with hypercholesterolemic diet the normal coronary vaso dilator response to serotonin is replaced by vasoconstriction sensitiv e to 5HT2 receptor blockade. These experiments were designed to determ ine the receptor subtype involved in the contractile response of large isolated coronary arteries (without endothelium) taken from control a nd atherosclerotic rabbits. In both tissues the agonists' rank potency was 5-carboxamidotryptamine > serotonin (5HT)> sumatriptan > 8-OHDPAT : (+/-)-8-Hydroxydipropylaminotetralin HBr > 2-methylserotonin, In art eries from young rabbits, 5HT and sumatriptan induced contractions whi ch were not influenced by ketanserin up to 3 x 10(-8) M. However, the 5HT2 antagonist at the concentration of 10(-6) M induced a significant rightward shift of the concentration-response curves. The contraction s to the two serotoninergic agonists were competitively inhibited by m ethiothepin. NAN 190, a 5HT1A antagonist, LY 53857, a 5HT1C and 5HT2 a ntagonist, cyanopindolol, a 5HT1A and 5HT1B antagonist and ICS 205-930 , a 5HT3 and 5HT4 antagonist (up to 10(-6) M) did not inhibit the cont ractile response to 5HT. Rauwolscine (10(-6) M) significantly shifted the concentration-response curves to the two agonists. Very similar re sults were obtained in coronary arteries from atherosclerotic rabbits. These data demonstrate that in rabbit epicardial coronary artery smoo th muscle, the receptor involved in the serotoninergic response is a 5 HT1-like subtype, possibly a 5HT1D. In this preparation, under our exp erimental conditions, there was no evidence for the presence of 5HT2 r eceptors. The induction of atherosclerosis did not induce significant changes in the serotoninergic response in these large coronary arterie s, illustrating the marked heterogeneity between microvasculature and large arteries in the rabbit heart.