Different receptors for angiotensin II at pre‐ and postjunctional level of the canine mesenteric and pulmonary arteries

Abstract

1 This investigation was undertaken to compare pre-and postjunctional receptors involved in the responses of the canine mesenteric and pulmonary arteries to angiotensin II. 2 In the mesenteric artery, angiotensin II caused an enhancement of tritium over¯ow evoked by electrical stimulation (EC 30% =5 nM), the maximal eect representing an increase by about 45%. Postjunctionally, angiotensin II caused concentration-dependent contractions (pD 2 =8.57). Saralasin antagonized both pre-and postjunctional eects of angiotensin II, but it was more potent at post-than at prejunctional level (pA 2 of 9.51 and 8.15, respectively), while losartan antagonized exclusively the postjunctional eects of angiotensin II (pA 2 =8.15). PD123319 had no antagonist eect either pre-or postjunctionally. 3 In the pulmonary artery, angiotensin II also caused an enhancement of the electrically-evoked tritium over¯ow (EC 30% =1.54 nM), its maximal eect increasing tritium over¯ow by about 80%. Postjunctionally, angiotensin II caused contractile responses (pD 2 =8.52). As in the mesenteric artery, saralasin antagonized angiotensin II eects at both pre-and postjunctional level and it was more potent postjunctionally (pA 2 of 9.58 and 8.10, respectively). Losartan antagonized only the postjunctional eects of angiotensin II (pA 2 =7.96) and PD123319 was ineective. 4 It is concluded that in both vessels: (1) pre-and postjunctional receptors belong to a dierent subtype, since they are dierently antagonized by the same antagonists; (2) postjunctional receptors belong to AT 1 subtype, since they are blocked by losartan but not by AT 2 antagonists; (3) prejunctional receptors apparently belong to neither AT 1 or AT 2 subtype since they are blocked by neither AT 1 nor AT 2 antagonists.

Angiotensin-Induced Enhancement of Excitatory Junction Potentials Evoked by Periarteriolar Nerve Stimulation and Vasoconstriction in Rat Mesenteric Arteries Are Both Mediated by the Angiotensin AT1 Receptor

“…Only eprosartan inhibited responses to sympathetic nerve stimulation, leading to the suggestion that eprosartan was a more effective inhibitor of sympathetic nervous system activity than the other AT1 antagonists, presumably by blocking activation of the pre-junctional AT1 receptor by endogenous AngII [29]. The failure of losartan to reduce the response to sympathetic nerve stimulation is consistent with reports in the canine mesenteric and pulmonary arteries, where the AngIIinduced enhancement of electrically stimulated noradrenaline release was not antagonized by losartan [8]. The reasons for the apparent differential sensitivity of pre-junctional AngII receptors to the AT1 antagonists, and losartan in particular, remains to be established but may relate to the AT1 receptor subtype involved.…”

“…Thus, in guinea pig isolated atria the enhancement of noradrenaline release by AngII is blocked by losartan, indicating that the pre-junctional receptor located on the sympathetic nerves is of the AT1 subtype [7]. In contrast, in dog pulmonary and coronary artery, neither losartan nor PD 123319 blocked the enhancement of noradrenaline release by AngII whereas only losartan blocked the vasoconstrictor action of AngII [8]. In the rat tail artery, the vasoconstrictor effect of AngII was also blocked by losartan but in this case both antagonists blocked the facilitatory effect of AngII on noradrenaline release [9].…”

Differential effects of eprosartan and losartan at prejunctional angiotensin II receptors

“…After the response to a given concentration had reached the maximum, the tissue was repeatedly washed out. Desensitization has been reported when repeated additions of angiotensin II were made; indeed, in the canine pulmonary artery some desensitization was observed whenever the interval between two successive additions was less than 10 min (Guimarães et al 1998). To avoid this phenomenon, the additions of angiotensin II to the medium were made with intervals of at least 45 min.…”

“…On the basis of results obtained with selective AT 1 and AT 2 antagonists, the prejunctional effect of angiotensin II is considered as being mediated by AT 1 receptors in the majority of the tissues: canine kidney Suzuki et al 1992), guinea-pig atria (Brasch et al 1993), rabbit iris ciliary body (Ohia and Jumblatt 1993), rat atria (Gironacci et al 1994), human kidney (Rump et al 1995), rat trachea (Boicos et al 1998) and mouse atria (Cox et al 1999). However, on the same basis, there are also several tissues where the prejunctional receptors of angiotensin II cannot be classified as AT 1 : in the rat tail artery the effect of angiotensin II was inhibited to the same extent by selective AT l (losartan) and AT 2 (PD123319) antagonists (Cox et al 1995), and in the rat left ventricle (Moura et al 1997) as well as the canine mesenteric and pulmonary arteries (Guimarães et al 1998) the prejunctional effect of angiotensin II was not changed by selective concentrations of either antagonist. Similarly, in the rabbit vas deferens losartan was ineffective against the prejunctional effect of angiotensin II (Trachte et al 1990).…”

“…While it is generally accepted that the receptors mediating the direct postjunctional effect of angiotensin II at the effector organ are AT 1 (Dudley et al 1990;Rhaleb et al 1991;Cox et al 1995;Guimarães et al 1998), the situation is not so clear for the prejunctional effects for angiotensin II. On the basis of results obtained with selective AT 1 and AT 2 antagonists, the prejunctional effect of angiotensin II is considered as being mediated by AT 1 receptors in the majority of the tissues: canine kidney Suzuki et al 1992), guinea-pig atria (Brasch et al 1993), rabbit iris ciliary body (Ohia and Jumblatt 1993), rat atria (Gironacci et al 1994), human kidney (Rump et al 1995), rat trachea (Boicos et al 1998) and mouse atria (Cox et al 1999).…”