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 microM, 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 microM, 5-HT3) and SDZ 205-557 (1 microM, 5-HT4). In addition, cocaine (10 microM), pargyline (50 microM), prazosin (10 microM), indomethacin (3 microM) and SQ 29,548 (1 microM) 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), alpha-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 receptor subtype), and that the contraction mediated by 5-HT1-like receptors is enhanced in the basilar artery from SHRSP.
Nishimura
Y
Y
Department of Pharmacology, Kinki University School of Medicine, Osaka, Japan.
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology
D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012701:Serotonin; D013134:Spiperone; D008719:Methiothepin; D007650:Ketanserin