Angiotensin type 2 receptors mediate depressor phase of biphasic pressure response to angiotensin

Abstract

Angiotensin (ANG) can produce a biphasic arterial pressure response, i.e., an increase followed by a decrease. Because ANG type 1 (AT1) receptors mediate the pressor response to ANG, we hypothesized that the opposing depressor action is mediated by the ANG type 2 (AT2) receptors. In thiobutabarbital (Inactin)-anesthetized rats bolus injections of angiotensin III (ANG III; 100, 300, and 1,000 ng/kg iv) produced peak increases in MAP at 20 s of 13.4 +/- 1.4, 20.1 +/- 2, and 27.5 +/- 2.8 mmHg and maximum decreases in pressure at 120 s of -6.3 +/- 1.5, -6.8 +/- 2.2, and -11.4 +/- 4.9 mmHg. During blockade of the AT1 receptors with DuP 753 (losartan, 10 mg/kg) the increases in MAP were eliminated (P < 0.01), whereas the depressor responses (-24.7 +/- 8, -32.8 +/- 9.3, and -42.0 +/- 10.0 mmHg) were significantly (P < 0.05) larger. In separate groups of rats, combined blockade of both AT1 and AT2 receptors eliminated all changes in MAP in response to ANG III, whereas blockade of AT2 receptors alone enhanced the pressor response to ANG III. During AT1 receptor blockade angiotensin II also caused consistent decreases in pressure, which were inhibited during combined blockade of AT1 and AT2 receptors. Therefore, we have demonstrated that the AT2 receptors mediate a depressor response to ANG.

Role of bradykinins and nitric oxide in the AT2 receptor-mediated hypotension

“…The vasopressor response was mediated by angiotensin AT 1 while the vasodepressor response was related to angiotensin AT 2 receptors. 8 Furthermore, mice with targeted deletion of the AT 2 receptor is associated with vascular and renal hypersensitivity to angiotensin II, including sustained antidiuresis and hypertension. 39 Thus, the existence of an equilibrium between pressor AT 1 and depressor AT 2 receptor should be proposed.…”

“…It has been reported that angiotensin II can elicit a biphasic arterial pressure response in rabbits 7 and rats. 8 Furthermore, endothelium-dependent relaxations induced by angiotensin II have been reported in a variety of experimental preparations such as the fowl aorta 9 and canine renal and cerebral arteries. 10 The heterogeneity of the response to angiotensin II may be related to modulatory effects of the vascular endothelium or stimulation of different angiotensin II receptor subtypes.…”

“…Indeed, in anaesthetized rats blockade of angiotensin AT 2 receptors enhances the angiotensin-induced pressor response. 8 In addition, it has been shown that angiotensin II degradation products evoked endothelium-dependent relaxations in rat and rabbit cerebral arterioles, presumably through the activation of angiotensin AT 2 receptor subtypes. 11,12 Angiotensin II may act on angiotensin AT 2 receptor subtype, either directly or via the release of autacoids such as kinins and nitric oxide.…”

Receptors and their classification: focus on angiotensin II and the AT2 receptor

“…This effect is blocked by PD 123177. 98 Also, co-infusion of rats with Ang II and PD 123199 results in an enhanced blood pressure response as compared to rats infused with Ang II alone. 99 Although the AT 2 receptor seems to be involved in growth and differentiation, lack of a functional receptor still allows for development of an organism as illustrated by the establishment of AT 2 knockout mice strains.…”

Angiotensin II receptor pharmacology and AT1-receptor blockers

“…This effect is blocked by PD 123177. 88 Also, coinfusion of rats with Ang II and PD 123199 results in an enhanced blood pressure response, as compared to rats infused with Ang II alone. 89 Although the AT 2 receptor seems to be involved in growth and differentiation, lack of a functional receptor still allows for development of an organism, as illustrated by the establishment of AT 2 knockout mice strains.…”