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

Abstract

1 The effects of the AT, 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 gM) 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 /M) and unaffected by PD 123319 (0.1 uM), indicating that the vasoconstrictor action of angiotensin II is subserved by AT1 receptors.3 Angiotensin II (0.1-3 pM) produced concentration-dependent enhancement of both stimulationinduced (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 pM) 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 AT1 angiotensin II receptor antagonist, losartan (0.01 and 0.1 pM), reduced or abolished the enhancement of both S-I efflux and vasoconstrictor responses by 1 pM angiotensin II. 5 The combination of 0.01 pM losartan and 0.1 IM angiotensin II enhanced both the S-I efflux and stimulation-evoked vasoconstrictor response in caudal artery preparations from WKY rats, whereas 0.1 UM angiotensin alone was ineffective. The AT2 receptor antagonist PD 123319 (0.01 and 0.1 pM) 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 pM angiotensin II and PD 123319 (both 0.01 and 0.1 pM) enhanced S-I [3H]-noradrenaline efflux, whereas 0.1 pM angiotensin II alone was without effect. Moreover, losartan (0.1 pM) prevented the enhancement of S-I efflux by the combination of angiotensin II and PD 123319. 7 The present findings indicate that in the caudal artery of WKY and SH rats, and as previously found in Sprague-Dawley preparations, angiotensin II receptors similar to the ATIB subtype subserve enhancement of transmitter noradrenaline release. 8 As previously suggested for Sprague-Dawley caudal artery preparations, the synergistic prejunctional interaction of losartan and 0.1 pM angiotensin II in caudal artery preparations from WKY r...

Multiple prejunctional actions of angiotensin II on noradrenergic transmission in the caudal artery of the rat

“…Whilst the mechanism of the interaction remains obscure, it would appear to warrant further study. This is reinforced by our subsequent observations with caudal artery preparations from spontaneously hypertensive rats of a similar synergistic interaction between PD 123319, rather than losartan, and the relatively low concentration of angiotensin II (0.1 gM) (Cox et al, 1996).…”

“…Recently, we reported preliminary findings which indicated that angiotensin II exerted an action on transmitter noradrenaline release in the rat caudal artery which apparently opposed the well-known prejunctional facilitatory effect of the peptide (Cox et al, 1995b). Specifically, a low concentration of the AT,-selective antagonist losartan (0.01 4uM), was found to increase markedly the ability of angiotensin II to enhance the field stimulation-evoked efflux of [3H]-noradrenaline which had been incorporated into the noradrenergic transmitter stores of the artery.…”

“…In blood vessels angiotensin II also induces the release of endothelium-derived smooth muscle relaxing factors such al., 1988;Boulanger et al, 1995). These endothelium-derived products generally exert opposing influences to the facilitatory actions of angiotensin II on noradrenergic neuroeffector transmission (Malik, 1978;Ferrer et al, 1992;Boulanger et al, 1995).Recently, we reported preliminary findings which indicated that angiotensin II exerted an action on transmitter noradrenaline release in the rat caudal artery which apparently opposed the well-known prejunctional facilitatory effect of the peptide (Cox et al, 1995b In experiments in which the effects of angiotensin II and/or non-peptide angiotensin II antagonists were investigated, these drugs were introduced into the PSS 20 min before the second period of stimulation.In experiments in which the effects of indomethacin and Nwnitro-L-arginine methyl ester (L-NAME) were investigated, these drugs were introduced into the PSS 30 min before the first period of stimulation and were present for the remainder of the experiment. …”

“…Recently, we reported preliminary findings which indicated that angiotensin II exerted an action on transmitter noradrenaline release in the rat caudal artery which apparently opposed the well-known prejunctional facilitatory effect of the peptide (Cox et al, 1995b In experiments in which the effects of angiotensin II and/or non-peptide angiotensin II antagonists were investigated, these drugs were introduced into the PSS 20 min before the second period of stimulation.…”

Effects of the AT1 Antagonist HR 720 in Comparison to Losartan on Stimulated Sympathetic Outflow, Blood Pressure, and Heart Rate in Pithed Spontaneously Hypertensive Rats

“…Despite these pharmacological differences, both AT 1 antagonists are equally effective in inhibiting Ang-II-induced stimulation of catecholamine release, thus providing no further evidence for a different receptor subtype at vascular and neuronal sites. Subtypes of the AT 1 receptor, named AT 1A and AT 1B , exist in the rat [11], but they cannot be discriminated by losartan [11,37]. To date, there is only one report about HR 720 in the literature [17] which provides no information as to the AT 1 subtype specificity or a noncompetitive type of antagonism of HR 720.…”