Angiotensin II receptors involved in the enhancement of noradrenergic transmission in the caudal artery of the spontaneously hypertensive rat

1 The effects of the AT1 receptor antagonist losartan and the AT2 receptor antagonist PD 123319, on actions of angiotensin II in isolated caudal arteries of spontaneously hypertensive (SH) and age‐matched normotensive (Wistar‐Kyoto) rats were compared. 2 Angiotensin II (0.1–3 μm) produced concentration‐dependent increases in perfusion pressure in artery preparations from both SH and Wistar‐Kyoto (WKY) rats, the maximal increase in the SH rat being significantly greater than the increase in WKY rats. The increase in perfusion pressure in preparations from both strains of rats was prevented by losartan (0.1 μm) and unaffected by PD 123319 (0.1 μm), indicating that the vasoconstrictor action of angiotensin II is subserved by AT1 receptors. 3 Angiotensin II (0.1–3 μm) produced concentration‐dependent enhancement of both stimulation‐induced (S‐I) efflux of [3H]‐noradrenaline and stimulation‐evoked vasoconstrictor responses in isolated preparations of caudal artery from both SH and WKY rats, in which the noradrenergic transmitter stores had been labelled with [3H]‐noradrenaline. The maximum enhancement of S‐I efflux produced by angiotensin II (1 μm) was significantly greater in artery preparations from WKY rats than in preparations from SH rats, whereas the maximum enhancement of stimulation‐evoked vasoconstrictor responses was greater in preparations from SH rats than in those from WKY rats. 4 In artery preparations from both WKY and SH rats, the AT2 angiotensin II receptor antagonist, losartan (0.01 and 0.1 μm), reduced or abolished the enhancement of both S‐I efflux and vasoconstrictor responses by 1 μm angiotensin II. 5 The combination of 0.01 μm losartan and 0.1 μm angiotensin II enhanced both the S‐I efflux and stimulation‐evoked vasoconstrictor response in caudal artery preparations from WKY rats, whereas 0.1 μm angiotensin alone was ineffective. The AT2 receptor antagonist PD 123319 (0.01 and 0.1 μm) prevented the enhancement of both S‐I efflux and stimulation‐evoked vasoconstrictor responses by the combination of angiotensin II and losartan. 6 In contrast to findings in WKY preparations and those previously obtained for arteries from another normotensive strain (Sprague‐Dawley), in artery preparations from SH rats there was no synergistic interaction between losartan and angiotensin II. Rather, combinations of 0.1 μm angiotensin II and PD 123319 (both 0.01 and 0.1 μm) enhanced S‐I [3H]‐noradrenahne efflux, whereas 0.1 μm angiotensin II alone was without