A lower ratio of AT1/AT2 receptors of angiotensin II is found in female than in male spontaneously hypertensive rats

Silva-Antonialli, Michele Melo; Tostes, Rita C.; Fernandes, Liliam; Fior-Chadi, Débora Rejane; Akamine, Eliana Hiromi; Carvalho, Maria Helena Catelli de; Fortes, Zuleica Bruno; Nigro, Dorothy

doi:10.1016/j.cardiores.2004.01.020

Cited by 172 publications

(177 citation statements)

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“…25 Furthermore, estrogen inactivates reactive oxygen species like the vasodilator H 2 O 2 26,27 and alters the AT 1 /AT 2 receptor ratio. 28,29 Both phenomena will directly affect Ang II-induced vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

Nongenomic Effects of Aldosterone in the Human Heart

et al. 2005

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Abstract-Aldosterone exerts rapid "nongenomic" effects in various nonrenal tissues. Here, we investigated whether such effects occur in the human heart. Trabeculae and coronary arteries obtained from 57 heart valve donors (25 males; 32 females; 17 to 66 years of age) were mounted in organ baths. Aldosterone decreased contractility in atrial and ventricular trabeculae by maximally 34Ϯ3% and 15Ϯ4%, respectively, within 5 to 15 minutes after its application. The protein kinase C (PKC) inhibitor chelerythrine chloride, but not the mineralocorticoid receptor antagonists spironolactone and eplerenone, blocked this effect. Aldosterone also relaxed trabeculae that were prestimulated with angiotensin II (Ang II), and its negative inotropic effects were mimicked by hydrocortisone (at 10-fold lower potency) but not 17␤-estradiol. Aldosterone concentrations required to reduce inotropy were present in failing but not in normal human hearts. Previous exposure of coronary arteries to 1 mol/L aldosterone or 17␤-estradiol (but not hydrocortisone) doubled the maximum contractile response (E max ) to Ang II. ⌬E max correlated with extracellular signal-regulated kinase (ERK) 1/2 phosphorylation (PϽ0.01). Spironolactone and eplerenone did not block the potentiating effect of aldosterone. Studies in porcine renal arteries showed that potentiation also occurred at pmol/L aldosterone levels but not at 17␤-estradiol levels Ͻ1 mol/L. Aldosterone did not potentiate the ␣ 1 -adrenoceptor agonist phenylephrine. In conclusion, aldosterone induces a negative inotropic response in human trabeculae (thereby antagonizing the positive inotropic actions of Ang II) and potentiates the vasoconstrictor effect of Ang II in coronary arteries. These effects are specific and involve PKC and ERK 1/2, respectively. Furthermore, they occur in a nongenomic manner, and require pathological aldosterone concentrations.

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Section: Discussionmentioning

confidence: 99%

Nongenomic Effects of Aldosterone in the Human Heart

et al. 2005

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“…In a previous study, we found that impact of MasR on pressure natriuresis and diuresis was gender related, and in presence of MasR while AT1R and AT2R were blocked, pressure natriuresis and diuresis was augmented in male but not in female rats (22). Many putative mechanisms could participate in this interaction; including functional antagonism, crosstalk, or oligomerization (44), and other studies have explained the formation of heterodimers among different receptors (2,35). There are static heterodimers between the AT1R and bradykinin B 2 receptor, and between the AT1R and MasR that may increase activation of G protein (4,16,24,35).…”

Section: Discussionmentioning

confidence: 98%

“…Many putative mechanisms could participate in this interaction; including functional antagonism, crosstalk, or oligomerization (44), and other studies have explained the formation of heterodimers among different receptors (2,35). There are static heterodimers between the AT1R and bradykinin B 2 receptor, and between the AT1R and MasR that may increase activation of G protein (4,16,24,35). Therefore, it is not possible to explain the exact mechanism related to the tendency to an increase in RBF/KW by A779 in male rats.…”

Section: Discussionmentioning

confidence: 99%

“…AT1R causes vasoconstriction, cell multiplication, and sodium retention. It also attenuates glomerular filtration rate as well as it augments mesangial cell hypertrophy and renal damage, while AT2R and MasR disagrees with the AT1R functions (35,40). It is reported that MasR is an AT1R antagonist and Ang 1-7 / MasR straightly resists many actions of Ang II (38).…”

mentioning

confidence: 99%

“…It was also explained that the vasodilator effect of Ang 1-7 complicates the interaction of MasR with AT1R and AT2R in perfused mouse heart (7). Females have AT2R/ AT1R ratio higher than males (35), but MasR blockade or knockout of ACE2 can abolish sex difference in response to Ang II infusion in rats (38). Administration of MasR antagonist (A779) in female rats also equals the blood pressure response to Ang II in both genders (38).…”

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confidence: 99%

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Role of Mas receptor antagonist (A779) in renal hemodynamics in condition of blocked angiotensin II receptors in rats

Mansoori

Oryan

Nematbakhsh

2016

Acta Physiologica Hungarica

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The vasodilatory effect of angiotensin 1–7 (Ang 1-7) is exerted in the vascular bed via Mas receptor (MasR) gender dependently. However, the crosstalk between MasR and angiotensin II (Ang II) types 1 and 2 receptors (AT1R and AT2R) may change some actions of Ang 1-7 in renal circulation. In this study by blocking AT1R and AT2R, the role of MasR in kidney hemodynamics was described. In anaesthetized male and female Wistar rats, the effects of saline as vehicle and MasR blockade (A779) were tested on mean arterial pressure (MAP), renal perfusion pressure (RPP), renal blood flow (RBF), and renal vascular resistance (RVR) when both AT1R and AT2R were blocked by losartan and PD123319, respectively. In male rats, when AT1R and AT2R were blocked, there was a tendency for the increase in RBF/wet kidney tissue weight (RBF/KW) to be elevated by A779 as compared with the vehicle (P=0.08), and this was not the case in female rats. The impact of MasR on renal hemodynamics appears not to be sexual dimorphism either when Ang II receptors were blocked. It seems that co-blockade of all AT1R, AT2R, and MasR may alter RBF/ KW in male more than in female rats. These findings support a crosstalk between MasR and Ang II receptors in renal circulation.

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Sex Differences in Angiotensin II Hypertension

Sullivan

2015

Sodium and Water Homeostasis

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A lower ratio of AT1/AT2 receptors of angiotensin II is found in female than in male spontaneously hypertensive rats

Abstract: There is sexual dimorphism in vascular reactivity and in receptor gene expression to Ang II in SHR. We conclude that estrogen modulates AT(1) and AT(2) receptor gene expression and that this might explain at least partially the lower blood pressure observed in female SHR.

Cited by 172 publications

References 15 publications

Nongenomic Effects of Aldosterone in the Human Heart

Nongenomic Effects of Aldosterone in the Human Heart

Role of Mas receptor antagonist (A779) in renal hemodynamics in condition of blocked angiotensin II receptors in rats

Sex Differences in Angiotensin II Hypertension

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