Evidence for the involvement of different receptor subtypes the pre- and postjunctional actions of angiotensin Ⅱ at rat sympathetic neuroeffector sites

摘要

1. The effects of the nonpeptide angiotensin Ⅱ receptor (AT) antagonists losartan and PD 123319 on actions of angiotensin II in the rat caudal artery and rat vas deferens preparations were inves- tigated. 2. Angiotensin Ⅱ (1.0 μM) increased perfusion pressure in isolated segments of the rat caudal artery. This increase in perfusion pressure was prevented by the AT_1-antagonist, losartan (0.1 μM) but was not affected by the AT_2-antagonist, PD 123319 (0.1 μM). 3. Angiotensin Ⅱ (0.1-3.0 μM) produced a concentration-dependent enhancement of the stimulation-induced (S-I) efflux of [~3H]-noradrenaline from isolated segments of rat caudal artery in which the noradrenergic transmitter stores had been labelled with [~3H]-noradrenaline. The maximum enhancement of S-I efflux was approximately 60% with 1.0 μM angiotensin Ⅱ. 4. Losartan (0.01 and 0.1 μM) reduced the enhancement of S-I efflux produced by 1.0 μM angiotensin Ⅱ in the caudal artery. 5. PD 123319 (0.01 μM) did not affect the enhancement of S-I efflux produced by angiotensin Ⅱ (1.0 μM) in the caudal artery. However, in a higher concentration (0.1 μM), PD 123319 reduced the enhancement of S-I efflux produced by 1.0 μM angiotensin Ⅱ. 6. Angiotensin Ⅱ produced concentration-dependent enhancement of the purinergic twitch responses (1 pulse/60 s) in the rat vas deferens, 7. Losartan (0.03 μM) and PD 123319 (0.03 μM) each reduced the angiotensin Ⅱ-induced enhancement of the twitch responses in the rat vas deferens. 8. These findings indicate that the enhancement of sympathetic neuroeffector transmission in both the caudal artery and vas deferens of the rat involves angiotensin receptor subtype(s) sensitive to both losartan and PD 123319. In contrast, the direct vasoconstrictor effect of angiotensin Ⅱ in the rat caudal artery involves activation of a receptor subtype sensitive only to losartan.