Angiotensin AT2 receptors mediate vasodepressor response to footshock in rats

Israel, A; Cierco, Maria; Sosa, Beatríz Elena Parra

doi:10.1016/s0014-2999(00)00133-3

Cited by 30 publications

(19 citation statements)

References 26 publications

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“…Thus, in the cardiovascular system, Ang II-induced pressor response is coupled to the AT 1 receptor, whereas the vasodepressor response is coupled to the AT 2 receptor. 15 This observation is in agreement with studies that demonstrated the involvement of AT 2 receptors with vasodilatation. 15 Having demonstrated AT 1 and AT 2 receptors mediating qualitatively distinct responses in the kidney, we next explored whether alterations in Ang II receptor status may account for the greater vascular responses to Ang II in kidney failure.…”

supporting

confidence: 92%

Angiotensin II Type AT ₂ Receptor mRNA Expression and Renal Vasodilatation Are Increased in Renal Failure

Bautista

Sánchez²,

Hernández³

et al. 2001

Hypertension

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Abstract-Kidney failure is associated with changes in renal vascular responses to angiotensin (Ang) II. We characterized expression of Ang II receptors and the renal vasoconstrictor and vasodilator responses to Ang II in kidneys from sham-operated and kidney failure rats. In the isolated perfused kidney of sham-operated rats, Ang II (1, 2, 4, and 8 ng) increased perfusion pressure by 27Ϯ6, 41Ϯ10, 54Ϯ11, and 74Ϯ12 mm Hg, respectively. These responses were amplified by 62Ϯ10% (PϽ0.05) in kidney failure rats. Losartan (1 mol/L), an angiotensin type 1 (AT 1 ) receptor blocker, abolished renal vasoconstriction induced by Ang II, unmasking a renal vasodilatation that was greater in kidney failure rats. CGP-42112 (1 mol/L) or PD 123,319 (1 mol/L), angiotensin type 2 (AT 2 ) receptor ligands, blunted Ang II-induced renal vasodilatation. In the renal tissue of kidney failure rats, there was a marked increase in expression of AT 1 and AT 2 mRNA receptor. Ang II-induced vasodilatation was blunted by eicosatetraynoic acid (1 mol/L), the all-purpose inhibitor of arachidonic acid metabolism; clotrimazole (1 mol/L), an inhibitor of epoxygenase-dependent arachidonic acid metabolism; or N-nitro-L-arginine methyl ester (L-NAME; 1 mol/L), an inhibitor of NO synthesis.On stimulation with Ang II, 20-HETE was the predominant product released into the renal effluent of sham-operated rats, whereas epoxy-eicosatrienoic acids were the predominant products released into the effluent of kidney failure rats. These data suggest that during development of kidney failure, there is induction of the AT 2 receptors, which may account for increased Ang II-dependent vasodilatation through the predominant release of epoxyeicosatrienoic acids . Key Words: receptors, angiotensin Ⅲ cytochrome P450 Ⅲ kidney failure Ⅲ angiotensin II Ⅲ arachidonic acid T he kidney is an important target organ for angiotensin (Ang) II, where it plays a critical role in the regulation of kidney function. Two major isoforms of the Ang II receptor have been described: type 1 (AT 1 ) and type 2 (AT 2 ). 1 Most of the known effects of Ang II are attributable to the AT 1 receptor, 2 and little is known concerning the function of the AT 2 receptor. The AT 2 receptor is widely expressed in fetal tissues and decreases during development. 3 Renal AT 2 receptor was demonstrated to be involved in regulation of pressure natriuresis 4 and in preglomerular afferent arteriolar dilatation. 5 Also, a role was proposed for AT 2 receptor in vascular development. 6 Cytochrome P450 -derived arachidonic acid (CYP-AA) metabolites released in response to Ang II. 7 The biological activities of CYP-AA are potentially of great importance in renal function in view of the capacity of these metabolites to regulate various renal mechanisms. 8 Activation of the AT 2 receptor increases production of epoxygenase-derived metabolites in the rabbit afferent arteriole. 5 Furthermore, in the absence of AT 2 receptor, microsomal AA -hydroxylase activity was greatly reduced, suggesting that the capacity to produce...

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supporting

confidence: 92%

Angiotensin II Type AT ₂ Receptor mRNA Expression and Renal Vasodilatation Are Increased in Renal Failure

Bautista

Sánchez²,

Hernández³

et al. 2001

Hypertension

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“…In fact, some studies have demonstrated that the activation of AT 2 by Ang II can induce effects opposite to the AT 1 -mediated effects. A few studies, in rats, have suggested that Ang II has relaxant effects that are mediated by AT 2 receptors, thereby counteracting the constrictor action of Ang II at the smooth muscle site (Scheuer and Perrone, 1993;Israel et al, 2000).…”

Section: De Godoy and De Oliveiramentioning

confidence: 99%

“…It has been shown that the inhibitory AT 2 -mediated effect of Ang II may be mediated either directly or via the release of inhibitory autacoids such as NO (Siragy and Carey, 1997;Cote et al, 1998;Siragy et al, 1999;Israel et al, 2000). Since the rat anococcygeus smooth muscle has a rich nitrergic enervation, it may be postulated that the inhibitory AT 2 -mediated effect is mediated by NO production.…”

Section: De Godoy and De Oliveiramentioning

confidence: 99%

“…There is evidence that some of these actions are under inhibitory control by angiotensin AT 2 receptors. Indeed, AT 2 receptor subtypes antagonize both pressor and growth effects of the AT 1 receptor subtypes (Hein et al, 1995;Ichiki et al, 1995;Nakajima et al, 1995, Israel et al, 2000 and the centrally mediated Ang II-induced release of vasopressin and drinking (Höhle et al, 1995). Thus, the existence of an equilibrium between constrictor AT 1 and inhibitory AT 2 receptor could be proposed.…”

Section: De Godoy and De Oliveiramentioning

confidence: 99%

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Cross-Talk Between AT₁ and AT₂Angiotensin Receptors in Rat Anococcygeus Smooth Muscle

Godoy

Oliveira²

2002

J Pharmacol Exp Ther

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Schild regressions for the selective AT 1 and AT 2 receptor antagonists, losartan and PD123319 (S-[ϩ]-1-[(4-dimethylamino]-3-methylphenyl)methyl]-5- [diphenylacetyl]-4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridine-6-carboxilic acid), respectively, were calculated to analyze the heterogeneity of receptor populations in the rat anococcygeus muscle. For a one-receptor system, the Schild regression has a slope of unity and an intercept of K B for competitive antagonists. However, in a two-receptor system, a deviation from the single-receptor plot will occur. This is predicated on the assumption that the secondary receptor is less sensitive to the antagonist than the primary receptor. Results showed that the Schild regression for losartan did not produce a slope of unity, and PD123319 did not produce any effect. However, tissue incubation with losartan plus PD123319 resulted in a Schild regression that has a slope of unity and a pK B of 9.32. In the presence of prazosin, an ␣ 1 -adrenoceptor antagonist, losartan did not produce any effect. Conversely, PD123319 enhanced the angiotensin II (Ang II)-induced contraction in a concentration-dependent fashion, suggesting an inhibitory AT 2 -mediated effect. This effect was confirmed with assays that showed a relaxant response induced by Ang II on precontracted tissues incubated with prazosin. PD123319 and N G -nitro-L-arginine methyl ester [nitric-oxide (NO) synthase inhibitor)] markedly inhibited the relaxant response of Ang II. In contrast, losartan did not produce any significant effect. Consequently, results show that the mechanism underlying the AT 2 -mediated effect is highly dependent on NO generation. Results indicate the presence of a heterogeneous angiotensin receptor population in the rat anococcygeus muscle following a negative cross-talk relationship between the AT 1 and AT 2 subtypes.

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“…12,13 After drug treatment, the animals were transferred to a Plexiglas chamber with a copper rod floor where they received mild footshocks (2.0 Hz, 100 V, 5 ms, for 5 min) delivered by a Grass stimulator (Model S48). The rats were placed into the heating oven and after 10 min of heating, footshock-stimulation was performed inside the oven for a period of 5 min.…”

Section: Quantification Of Cardiovascular Responses To Footshocksmentioning

confidence: 99%

Angiotensin II supports sympathetically mediated vasopressor response to footshock-stress

Israel

Sosa-Canache

2002

J Hum Hypertens

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The present study was carried out to assess whether endogenous angiotensin II (Ang II) supports sympathetically mediated cardiovascular response to stress in conscious unrestrained rats, using experimental models in which the renin-angiotensin-system was reduced or blocked. Footshock-stress increased mean arterial pressure (MAP) and heart rate (HR). Inhibition of angiotensin-converting enzyme with captopril or blockade of AT 1 angiotensin receptor with losartan, attenuated vasopressor responses to footshocks, while heart rate response was not altered. Bilateral nephrectomy suppressed vasopressor response as well the elevation of

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Angiotensin AT2 receptors mediate vasodepressor response to footshock in rats

Cited by 30 publications

References 26 publications

Angiotensin II Type AT ₂ Receptor mRNA Expression and Renal Vasodilatation Are Increased in Renal Failure

Angiotensin II Type AT ₂ Receptor mRNA Expression and Renal Vasodilatation Are Increased in Renal Failure

Cross-Talk Between AT₁ and AT₂Angiotensin Receptors in Rat Anococcygeus Smooth Muscle

Angiotensin II supports sympathetically mediated vasopressor response to footshock-stress

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Angiotensin AT2 receptors mediate vasodepressor response to footshock in rats

Cited by 30 publications

References 26 publications

Angiotensin II Type AT 2 Receptor mRNA Expression and Renal Vasodilatation Are Increased in Renal Failure

Angiotensin II Type AT 2 Receptor mRNA Expression and Renal Vasodilatation Are Increased in Renal Failure

Cross-Talk Between AT1 and AT2Angiotensin Receptors in Rat Anococcygeus Smooth Muscle

Angiotensin II supports sympathetically mediated vasopressor response to footshock-stress

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Angiotensin II Type AT ₂ Receptor mRNA Expression and Renal Vasodilatation Are Increased in Renal Failure

Angiotensin II Type AT ₂ Receptor mRNA Expression and Renal Vasodilatation Are Increased in Renal Failure

Cross-Talk Between AT₁ and AT₂Angiotensin Receptors in Rat Anococcygeus Smooth Muscle