Rat angiotensin II receptor: cDNA sequence and regulation of the gene expression

Iwai, Naoharu; Yamano, Yoshiaki; Chaki, Shigeyuki; Konishi, Fumiko; Bardhan, Smriti; Tibbetts, Clark; Sasaki, Keisuke; Hasegawa, Mamoru; Matsuda, Yuzuru; Inagami, Tadashi

doi:10.1016/0006-291x(91)91982-i

Cited by 187 publications

(58 citation statements)

References 13 publications

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“…The present results indicate that the pressor effect of carbachol involves the central angiotensin system and AT1 receptor activation. The pressor effect of ANG II was previously shown to depend on AT1 receptor activation (6,15) and our data confirm these results (6,15,16). Ramipril is an angiotensin-converting enzyme inhibitor acting as a prodrug, and the present results suggest that this drug may be implicated in the pressor response induced by central cholinergic activation.…”

supporting

confidence: 92%

Functional evidence that the central renin-angiotensin system plays a role in the pressor response induced by central injection of carbachol

Saad

Luiz²,

Camargo³

et al. 1997

Braz J Med Biol Res

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We investigated the effects of losartan, an AT 1 -receptor blocker, and ramipril, a converting enzyme inhibitor, on the pressor response induced by angiotensin II (ANG II) and carbachol (a cholinergic receptor agonist). Male Holtzman rats (250-300 g) with a stainless steel cannula implanted into the lateral ventricle (LV) were used. The injection of losartan (50 nmol/1 µl) into the LV blocked the pressor response induced by ANG II (12 ng/1 µl) and carbachol (2 nmol/1 µl). After injection of ANG II and carbachol into the LV, mean arterial pressure (MAP) increased to 31 ± 1 and 28 ± 2 mmHg, respectively. Previous injection of losartan abolished the increase in MAP induced by ANG II and carbachol into the LV (2 ± 1 and 5 ± 2 mmHg, respectively). The injection of ramipril (12 ng/1 µl) prior to carbachol blocked the pressor effect of carbachol to 7 ± 3 mmHg. These results suggest an interaction between central cholinergic pathways and the angiotensinergic system in the regulation of arterial blood pressure.

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supporting

confidence: 92%

Functional evidence that the central renin-angiotensin system plays a role in the pressor response induced by central injection of carbachol

Saad

Luiz²,

Camargo³

et al. 1997

Braz J Med Biol Res

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“…The sheep AT, receptor partial cDNA sequence from nucleotide 114 to 783 is presented in Figure 1 and compared with corresponding AT, cDNA sequences from other species. This sequence is 99% homologous with bovine AT, (28), 94% with pig AT, (32), 92% with human AT, (33,34), 87% with rat AT,, (35)(36)(37), and 86% with rat AT,, (35,38). The Figure 1.…”

Section: Resultsmentioning

confidence: 88%

Ontogenic Changes and Regulation of Renal Angiotensin II Type 1 Receptor Gene Expression during Fetal and Newborn Life

et al. 1994

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Factors regulating the expression of the angiotensin I1 subtype 1 (AT,) receptor during fetal life have not been investigated previously. The present study was designed 1) to characterize the ontogeny of AT, receptor gene expression in the kidney of fetal and newborn sheep and 2) to determine the influence of both glucocorticoids and renal nerves in modulating AT, gene expression during fetal life and during the transition from fetal to newborn life. We first isolated and cloned a PCR product that has 98 and 94% homology with the cDNA encoding the bovine and pig AT, receptors, respectively, and 99 and 98% homology with the corresponding deduced protein sequences. Probing with this cDNA, we demonstrated that renal AT, mRNA expression did not change significantly during the last trimester of gestation in fetal sheep or immediately after birth but decreased significantly 10 d after birth. We also demonstrated that renal denervation in the fetus had no effect on renal AT, gene expression in 24-h-old newborn lambs. On the other hand, we observed in 130-d twin fetuses that a continuous intraperitoneal infusion (1 mL/h) of cortisol (3 mg/h or 6.2 p,mol/h) for 48 h in one of the twins increased the fetal plasma cortisol concentration from 32.0 + 7.1 to 1126 r 231 nmol/L and produced a significant decrease ( p < 0.005) in renal AT, gene expression compared with the control twin receiving an intraperitoneal infusion of 0.9% NaCl. In summary, this study demonstrates that renal AT, gene expression is elevated during fetal life and decreases after birth. It is also shown that glucocorticoids, but not renal nerves, contribute to the regulation of renal AT, gene expression during development. (Pediatr Res 36: 755-762, 1994)Abbreviations RAS, renin-angiotensin system AII, angiotensin I1 AT,, angiotensin I1 subtype 1 receptor AT,, angiotensin I1 subtype 2 receptor PCR, polymerase chain reaction RSNA, renal sympathetic nerve activity PRA, plasma renin activity rRNA, ribosomal RNA It has become apparent that the physiologic role of the RAS changes during embryonic and fetal maturation (1-4). Early during development, the RAS exerts a major influence o n cellular growth and organ differentiation (3-6). It is only later during fetal life that the RAS becomes an important modulator of blood pressure and distinct A11 receptor subtypes (AT, and AT,) (3, 9, 10). The AT, receptor subtype is expressed early during embryonic life in the rat (11,12), predominates in the fetal mesenchyme (3), and shows a marked decrease in expression during fetal and postnatal maturation (3). On the other hand, the AT, receptor subtype appears later during fetal development in the rat (3, 9, 10) and seems t o b e localized mainly in areas related t o blood pressure regulation and fluid homeostasis (3). Recent studies in rats have also shown that the AT, receptor gene is expressed in the fetal kidney, liver, adrenal, and heart and that the expression of this gene is developmentally regulated (9, lo), in agreement with previous A11 radioligand and in situ rece...

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“…Normalisation of blood pressure with AT1 receptor blockers regressed cardiac hypertrophy and completely reversed the increase in receptor message and density. In the adrenal gland, Iwai et al [39] confirmed this relationship between AT1 receptor expression and RAS activity, showing that administration of AT1 receptor blockers reduced the level of AT1 receptor mRNA, whereas the prolonged infusion of angiotensin II increased the expression level of this receptor mRNA.…”

Section: Discussionmentioning

confidence: 89%

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin–angiotensin system

et al. 2006

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Aims/hypothesis The angiotensin II (type 1) (AT1) receptor mediates many biological effects of the renin-angiotensin system (RAS), leading to remodelling of cardiac tissue. The present study was designed to analyse changes in the function and expression of the AT1 receptor as principal effector of the RAS in myocardium from type 2 diabetic patients compared with non-diabetic myocardium as control. In addition, we determined the effect of treatment with ACE inhibitors or AT1 receptor blockers on expression levels of the receptor in diabetic patients. Methods Gene expression of the AT1 receptor was analysed by quantitative RT-PCR and protein expression was determined by immunoblot analysis in human right atrial myocardium. We investigated functional coupling of the receptors by measuring contractility in isolated trabeculae stimulated with increasing concentrations of angiotensin II. Results Diabetic myocardium showed a significant increase in protein expression (170±16% of control) and median mRNA expression (186% of control) of the AT1 receptor.The additional receptors were functionally coupled, resulting in a stronger inotropic response upon stimulation with angiotensin II (89±5.5% vs 29±1.6% in controls), whereas receptor affinity was similar in both groups. However, myocardium from diabetic patients treated with ACE inhibitors or AT1 receptor blockers showed no increase in AT1 receptor expression. Conclusions/interpretation AT1 receptor expression in myocardium of type 2 diabetic patients is dynamic, depending on the level of glycaemic control and the activity of the RAS. These findings could at least in part explain the strong therapeutic benefit of RAS inhibition in diabetic patients.

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Rat angiotensin II receptor: cDNA sequence and regulation of the gene expression

Cited by 187 publications

References 13 publications

Functional evidence that the central renin-angiotensin system plays a role in the pressor response induced by central injection of carbachol

Functional evidence that the central renin-angiotensin system plays a role in the pressor response induced by central injection of carbachol

Ontogenic Changes and Regulation of Renal Angiotensin II Type 1 Receptor Gene Expression during Fetal and Newborn Life

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin–angiotensin system

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