Characterization of 5‐hydroxytryptamine receptors mediating contractions in basilar arteries from stroke‐prone spontaneously hypertensive rats

1 The 5‐hydroxytryptamine (5‐HT) induced‐contraction in ring preparations of basilar arteries from Wistar‐Kyoto rats (WKY) and stroke‐prone spontaneously hypertensive rats (SHRSP) was pharmacologically characterized in vitro. 2 Contractile responses to 5‐HT (1 nM − 100 nM) and their pD2 values in arteries from SHRSP at 6 months of age were significantly greater than those in age‐matched WKY, although the maximum response did not differ between the two groups. 3 There were no significant differences in contractile responses to U‐44619, endothelin‐1, neuropeptide Y, and angiotensin II between WKY and SHRSP arteries. 4 Spiperone (1 nM − 1 μ, a 5‐HT2 receptor antagonist), produced biphasic displacement of the 5‐HT curves in WKY and SHRSP arteries. The response to high concentrations of 5‐HT was concentration‐dependently antagonized by spiperone, while the response to low concentrations of 5‐HT was resistant to blockade by spiperone, and the spiperone‐resistant contractile responses induced by 5‐HT were greater in SHRSP than in WKY. Ketanserin (1 − 100 nM, 5‐HT2) also produced a biphasic shift of the 5‐HT curves for both arteries. 5 Methiothepin (10 and 100 nM, 5‐HT1 and 5‐HT2) potently inhibited 5‐HT‐induced contractions in both groups. In addition, methiothepin (100 nM) produced a parallel shift to the right of the component of 5‐HT‐induced contractile responses that was resistant to blockade by spiperone in both groups. 6 The contractile effects of 5‐HT in WKY and SHRSP arteries were not affected by MDL 72222 (1 μ, 5‐HT3) and SDZ 205–557 (1 μ, 5‐HT4). In addition, cocaine (10 μ), pargyline (50 μ), prazosin (10 μ), indomethacin (3 μ) and SQ 29,548 (1 μ) did not affect the contractile effects of 5‐HT in either artery. 7 Contractile responses to 5‐carboxamidotryptamine, CGS 12066B, pindolol and propranolol were greater in SHRSP arteries than in WKY arteries, whereas contractions in response to 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT), α‐methyl‐5‐HT and 2‐methyl‐5‐HT did not differ between the two groups. Cisapride failed to contract basilar arteries in both groups. Furthermore, a correlation analysis showed a highly significant correlation between the pD2 values of 5‐HT agonists in WKY and SHRSP arteries and their published binding affinities at the 5‐HT1B subtype. 8 These findings suggest that 5‐HT elicits vasoconstriction in rat basilar arteries by stimulation of a mixed receptor population of 5‐HT2 and 5‐HT1‐like receptors (similar to the 5‐HT1B re