Developmental changes in AT1 and AT2 receptor-protein expression in rats

Abstract

It has long been known that angiotensin type-1 receptors (AT1R) play a critical role in sympathetic regulation, cardiovascular activity, and hormone secretion under physiological and pathological states. On the other hand, the functional significance of angiotensin type-2 receptors (AT2R) is poorly understood. In a recent study we demonstrated that, in rats with chronic heart failure, AT1R protein expression was increased but AT2R expression was decreased in the rostral ventrolateral medulla (RVLM). This imbalance of angiotensin receptors contributed to sympatho-excitation in the heart failure state. In the current experiment, we measured AT1R and AT2R protein expressions in the brainstem, kidney and liver from male foetuses (3 days before birth), male neonates (3 days after birth), male and female adults (8 weeks) and male aged (28 months) rats by Western blot analysis. In the brainstem, we found that the foetuses and neonates exhibited a significantly lower AT2R protein expression compared with adult rats (foetus 0.08 ± 0.01, neonate 0.12 ± 0.01, male adult 0.25 ± 0.01, female adult 0.22 ± 0.02; n = 4 per group, p < 0.001 foetus and neonate compared with male or female adults). In contrast, the foetuses and neonates expressed significantly higher AT1R protein than that of the adults (foetus 0.64 ± 0.09, neonate 0.56 ± 0.01, male adult 0.13 ± 0.02, female adult 0.08 ± 0.02; n = 4 each group, p < 0.001 foetus and neonate compared with male and female adults). In the liver, the AT2R protein was also higher in foetus and neonate, than in adult rats. Interestingly, the foetal liver expressed higher AT1R protein compared with that of the neonate. In the kidney, AT2R expression was significantly increased with age (foetus 0.08 ± 0.01, neonate 0.19 ± 0.02, male adult 0.49 ± 0.04, female adult 0.90 ± 0.10; n = 4 per group, p < 0.01–0.001). AT1R expression, on the other hand, was higher in the foetuses than that in both neonate and male adults. This study provides data contrary to existing dogma that AT2R expression is higher in foetal life and low in adults, suggesting an involvement of a potentially important functional role for AT2R in adult animals and AT1R in foetal development and/or physiology.

Testosterone downregulates angiotensin II type-2 receptor via androgen receptor-mediated ERK1/2 MAP kinase pathway in rat aorta

“…35,36 In the present study, we observed that AT 2 R expression is higher in females compared to males, consistent with the reports in the brain, kidney, and liver. 12–14 However, in contrast, spontaneously hypertensive rats (SHR) showed no sex-dependent differences in AT 2 R expression in aorta and mesenteric arteries. 17 The reason for the apparent discrepancies between the above study and the present study is not entirely clear.…”

Reporter mouse strain provides a novel look at angiotensin type-2 receptor distribution in the central nervous system

“…It has long-been assumed that the expression and function of AT2R predominates during development, while that of AT1R prevails during adulthood (Nuyt et al 1999; Yu et al 2010). As a consequence, the role of AT2R in adults has often been over-looked.…”

“…This likely stems from a number of reports that have indicated that AT2R expression predominates during development, while the expression of AT1R predominates during adulthood (Grady et al 1991; Ichiki and Inagami 1995; Nuyt et al 1999; Yu et al 2010) . Nonetheless, there are lines of evidence indicating that the brains of adult rodents densely express functional AT2Rs (Gao et al 2012; Hauser et al 1998; Lenkei et al 1996; Lenkei et al 1997) and that AT2R activation, in many instances, counteracts AT1R activation (Sumners et al 2013).…”

Brain-Targeted Angiotensin-Converting Enzyme 2 Overexpression Attenuates Neurogenic Hypertension by Inhibiting Cyclooxygenase-Mediated Inflammation

“…29 In addition, in heart failure rats with chronic elevation of pro-inflammatory cytokines, COX-1 was not altered but COX-2 was increased in the PVN. 41 A recent study also suggests that systemic inflammation activates microglia in RVLM to induce COX-2-dependent neuro-inflammation leading to an increase in oxidative stress that contributes to neurogenic hypertension. 42 Together, these studies highlight the importance of COX expression in the manifestation of a variety of disease conditions including neurogenic hypertension.…”