EVIDENCE FOR THE INVOLVEMENT OF DIFFERENT RECEPTOR SUBTYPES IN THE PREJUNCTIONAL AND POSTJUNCTIONAL ACTIONS OF ANGIOTENSIN-II AT RAT SYMPATHETIC NEUROEFFECTOR SITES

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 investigated. 2 Angiotensin II (1.0 mu M) 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 mu M) but was not affected by the AT(2)-antagonist, PD 123319 (0.1 mu M). 3 Angiotensin II (0.1-3.0 mu M) produced a concentration-dependent enhancement of the stimulation-induced (S-I) efflux of [H-3]-noradrenaline from isolated segments of rat caudal artery in which the noradrenergic transmitter stores had been labelled with [H-3]-noradrenaline. The maximum enhancement of S-I efflux was approximately 60% with 1.0 mu M angiotensin II. 4 Losartan (0.01 and 0.1 mu M) reduced the enhancement of S-I efflux produced by 1.0 mu M angiotensin II in the caudal artery. 5 PD 123319 (0.01 mu M) did not affect the enhancement of S-I efflux produced by angiotensin II (1.0 mu M) in the caudal artery. However, in a higher concentration (0.1 mu M), PD 123319 reduced the enhancement of S-I efffux produced by 1.0 mu M angiotensin II. 6 Angiotensin II produced concentration-dependent enhancement of the purinergic twitch responses (1 puIse/60 s) in the rat vas deferens. 7 Losartan (0.03 mu M) and PD 123319 (0.03 mu M) 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.