Mechanisms underlying the contractile responses to doxazosin enantiomers in the rat isolated atrium

Aim To study the mechanisms of inotropic responses to doxazosin enantiomers in the isolated rat atrium. Methods We analyzed the positive inotropic response to(-) doxazosin and the negative inotropic response to(+) doxazosin in the left atrium of rat using receptor-pharmacological technique. Results In the preparation treated with verapamil,the positive inotropic responses to 3 μmol·L- 1(-) doxazosin were significantly inhibited from the control level(245. 71 ±44. 29) mg to(172. 50 ± 43. 34) mg,(P 0. 05). In the preparation treated with methylene blue,the positive inotropic responses to 3 μmol·L- 1(-) doxazosin were significantly potentiated from the control level(245.71 ±44.29) mg to(303.33 ±45.90) mg,(P 0. 05). In the preparation treated with H-89,the positive inotropic responses to 3,10 and 30 μmol ·L- 1(-) doxazosin were(338. 57 ± 96.86) mg,(471.43 ±107.61) mg and(520.00 ±103. 44) mg,which were significantly(P 0. 05 ~ 0. 01) larger than the control levels of(245. 71 ± 44. 29) mg,(314. 29± 90. 34) mg and(357. 14 ± 68. 49) mg. Treatment with phenoxybenzamine,atropine,propranolol or indomethacin did not significantly affect the responses to doxazosin enantiomers. Conclusion The positive inotropic responses to(-) doxazosin in the isolated left atrium of rat are partially involved in L-type Ca2 +channels and intracellular cGMP level. However,α-adrenoceptors,muscarinic receptors,β-adrenoceptors and cyclooxygenases are not related to the responses to doxazosin enantiomers.