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Prepubertal angiotensin blockade exerts long-term therapeutic effect through sustained ATRAP activation in salt-sensitive hypertensive rats.
J Hypertens. 2011 Oct; 29(10):1919-29.JH

Abstract

OBJECTIVE

We previously showed that the molecule interacting with Ang II type 1 receptor (AT1R), ATRAP, promotes AT1R internalization and attenuates AT1R-mediated pathological responses. In this study we examined whether the regulation of renal ATRAP expression is related to the development of salt-induced hypertension and renal injury as well as to the beneficial effects of AT1R blockade.

METHODS AND RESULTS

Dahl Iwai salt-sensitive hypertensive and Dahl Iwai salt-resistant rats were divided into six groups for the administration of vehicle or olmesartan either continuously from 3 to 16 weeks, or transiently from weaning to puberty (3-10 weeks), and fed high salt diet from 6 to 16 weeks. In Dahl Iwai salt-sensitive rats, not only continuous, but also prepubertal olmesartan treatment improved hypertension at 15 weeks. Renal ATRAP expression was suppressed in vehicle-treated Dahl Iwai salt-sensitive rats, concomitant with up-regulation of renal oxidative stress, inflammation and fibrosis-related markers such as p22phox, TGF-β, fibronectin, monocyte chemotactic protein-1 and type 1 collagen. However, prepubertal as well as continuous olmesartan treatment recovered the suppressed renal ATRAP expression and inhibited the renal activation of p22phox, TGF-β, fibronectin, MCP-1 and type 1 collagen. In Dahl Iwai salt-resistant rats, such suppression of renal ATRAP expression or induction of renal pathological responses by salt loading was not observed.

CONCLUSIONS

These results indicate that prepubertal transient blockade of AT1R signaling exerts a long-term therapeutic effect on salt-induced hypertension and renal injury in Dahl Iwai salt-sensitive rats, partly through a sustained enhancement of renal ATRAP expression, thereby suggesting ATRAP a novel molecular target in salt-induced hypertension and renal injury.

Authors+Show Affiliations

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21844822

Citation

Dejima, Toru, et al. "Prepubertal Angiotensin Blockade Exerts Long-term Therapeutic Effect Through Sustained ATRAP Activation in Salt-sensitive Hypertensive Rats." Journal of Hypertension, vol. 29, no. 10, 2011, pp. 1919-29.
Dejima T, Tamura K, Wakui H, et al. Prepubertal angiotensin blockade exerts long-term therapeutic effect through sustained ATRAP activation in salt-sensitive hypertensive rats. J Hypertens. 2011;29(10):1919-29.
Dejima, T., Tamura, K., Wakui, H., Maeda, A., Ohsawa, M., Kanaoka, T., Haku, S., Kengo, A., Masuda, S., Shigenaga, A., Azuma, K., Matsuda, M., Yabana, M., Hirose, T., Uchino, K., Kimura, K., Nagashima, Y., & Umemura, S. (2011). Prepubertal angiotensin blockade exerts long-term therapeutic effect through sustained ATRAP activation in salt-sensitive hypertensive rats. Journal of Hypertension, 29(10), 1919-29. https://doi.org/10.1097/HJH.0b013e32834a5a46
Dejima T, et al. Prepubertal Angiotensin Blockade Exerts Long-term Therapeutic Effect Through Sustained ATRAP Activation in Salt-sensitive Hypertensive Rats. J Hypertens. 2011;29(10):1919-29. PubMed PMID: 21844822.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prepubertal angiotensin blockade exerts long-term therapeutic effect through sustained ATRAP activation in salt-sensitive hypertensive rats. AU - Dejima,Toru, AU - Tamura,Kouichi, AU - Wakui,Hiromichi, AU - Maeda,Akinobu, AU - Ohsawa,Masato, AU - Kanaoka,Tomohiko, AU - Haku,Sona, AU - Kengo,Azushima, AU - Masuda,Shin-Ichiro, AU - Shigenaga,Atsu-Ichiro, AU - Azuma,Koichi, AU - Matsuda,Miyuki, AU - Yabana,Machiko, AU - Hirose,Tomonori, AU - Uchino,Kazuaki, AU - Kimura,Kazuo, AU - Nagashima,Yoji, AU - Umemura,Satoshi, PY - 2011/8/17/entrez PY - 2011/8/17/pubmed PY - 2012/1/17/medline SP - 1919 EP - 29 JF - Journal of hypertension JO - J. Hypertens. VL - 29 IS - 10 N2 - OBJECTIVE: We previously showed that the molecule interacting with Ang II type 1 receptor (AT1R), ATRAP, promotes AT1R internalization and attenuates AT1R-mediated pathological responses. In this study we examined whether the regulation of renal ATRAP expression is related to the development of salt-induced hypertension and renal injury as well as to the beneficial effects of AT1R blockade. METHODS AND RESULTS: Dahl Iwai salt-sensitive hypertensive and Dahl Iwai salt-resistant rats were divided into six groups for the administration of vehicle or olmesartan either continuously from 3 to 16 weeks, or transiently from weaning to puberty (3-10 weeks), and fed high salt diet from 6 to 16 weeks. In Dahl Iwai salt-sensitive rats, not only continuous, but also prepubertal olmesartan treatment improved hypertension at 15 weeks. Renal ATRAP expression was suppressed in vehicle-treated Dahl Iwai salt-sensitive rats, concomitant with up-regulation of renal oxidative stress, inflammation and fibrosis-related markers such as p22phox, TGF-β, fibronectin, monocyte chemotactic protein-1 and type 1 collagen. However, prepubertal as well as continuous olmesartan treatment recovered the suppressed renal ATRAP expression and inhibited the renal activation of p22phox, TGF-β, fibronectin, MCP-1 and type 1 collagen. In Dahl Iwai salt-resistant rats, such suppression of renal ATRAP expression or induction of renal pathological responses by salt loading was not observed. CONCLUSIONS: These results indicate that prepubertal transient blockade of AT1R signaling exerts a long-term therapeutic effect on salt-induced hypertension and renal injury in Dahl Iwai salt-sensitive rats, partly through a sustained enhancement of renal ATRAP expression, thereby suggesting ATRAP a novel molecular target in salt-induced hypertension and renal injury. SN - 1473-5598 UR - https://www.unboundmedicine.com/medline/citation/21844822/Prepubertal_angiotensin_blockade_exerts_long_term_therapeutic_effect_through_sustained_ATRAP_activation_in_salt_sensitive_hypertensive_rats_ L2 - http://dx.doi.org/10.1097/HJH.0b013e32834a5a46 DB - PRIME DP - Unbound Medicine ER -