Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in doca-salt hypertension effects of atrial natriuretic polypeptide monoclonal antibody

Hiroshi Itoh; Kazuvoa Nakao; Masashi Mukoyama; Hiroshi Arai; Takayuki Yamada; Yoshihiko Saito; Shozo Shiono; Kiminori Hosoda; Gotaro Shirakami; Sinichi Suga; Hiroo Imura

doi:10.1093/ajh/4.1.39

Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in doca-salt hypertension effects of atrial natriuretic polypeptide monoclonal antibody

Hiroshi Itoh, Kazuvoa Nakao, Masashi Mukoyama, Hiroshi Arai, Takayuki Yamada, Yoshihiko Saito, Shozo Shiono, Kiminori Hosoda, Gotaro Shirakami, Sinichi Suga, Hiroo Imura

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5 Citations (Scopus)

Abstract

To elucidate the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in hypertension, we investigated the biosynthesis and secretion of ANP in deoxycorticosterone acetate (DOCA)-salt hypertensive rats and also examined the effect of passive immunization with monoclonal antibody raised against a-rat ANP on the development of hypertension in DOCA-salt rats. The plasma ANP level in DOCA-salt rats was significantly elevated in comparison to control rats. While the atrial ANP concentration in DOCA-salt rats was not significantly altered, the atrial level of ANPmRNA in DOCA-salt rats was two-fold higher than that in control rats. These results suggest the augmented biosynthesis of ANP in the atrium and the oversecretion of ANP from the heart in DOCA- salt rats. The levels of ANP and ANPmRNA in the ventricle of DOCA-salt rats exhibited significant increases, compared with those in control rats, suggesting the induction of ANP gene expression in the ventricle of DOCA-salt hypertensive rats under pre/after overload. Weekly intravenous administrations of monoclonal antibody with high affinity for a-rat ANP significantly augmented the rise in blood pressure of DOCA-salt rats. These results support the hypothesis that the augmented secretion of ANP is one of the defensive mechanisms to counteract high arterial pressure in this model of hypertension.

Original language	English
Pages (from-to)	39-41
Number of pages	3
Journal	American journal of hypertension
Volume	4
Issue number	1
DOIs	https://doi.org/10.1093/ajh/4.1.39
Publication status	Published - 1991 Apr
Externally published	Yes

Keywords

Atrial natriuretic polypeptide
DOCA- salt hypertension
Messenger RNA
Monoclonal antibody
Passive immunization

ASJC Scopus subject areas

Internal Medicine

Access to Document

10.1093/ajh/4.1.39

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Itoh, H., Nakao, K., Mukoyama, M., Arai, H., Yamada, T., Saito, Y., Shiono, S., Hosoda, K., Shirakami, G., Suga, S., & Imura, H. (1991). Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in doca-salt hypertension effects of atrial natriuretic polypeptide monoclonal antibody. American journal of hypertension, 4(1), 39-41. https://doi.org/10.1093/ajh/4.1.39

Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in doca-salt hypertension effects of atrial natriuretic polypeptide monoclonal antibody. / Itoh, Hiroshi; Nakao, Kazuvoa; Mukoyama, Masashi et al.

In: American journal of hypertension, Vol. 4, No. 1, 04.1991, p. 39-41.

Research output: Contribution to journal › Article › peer-review

Itoh, H, Nakao, K, Mukoyama, M, Arai, H, Yamada, T, Saito, Y, Shiono, S, Hosoda, K, Shirakami, G, Suga, S & Imura, H 1991, 'Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in doca-salt hypertension effects of atrial natriuretic polypeptide monoclonal antibody', American journal of hypertension, vol. 4, no. 1, pp. 39-41. https://doi.org/10.1093/ajh/4.1.39

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title = "Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in doca-salt hypertension effects of atrial natriuretic polypeptide monoclonal antibody",

abstract = "To elucidate the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in hypertension, we investigated the biosynthesis and secretion of ANP in deoxycorticosterone acetate (DOCA)-salt hypertensive rats and also examined the effect of passive immunization with monoclonal antibody raised against a-rat ANP on the development of hypertension in DOCA-salt rats. The plasma ANP level in DOCA-salt rats was significantly elevated in comparison to control rats. While the atrial ANP concentration in DOCA-salt rats was not significantly altered, the atrial level of ANPmRNA in DOCA-salt rats was two-fold higher than that in control rats. These results suggest the augmented biosynthesis of ANP in the atrium and the oversecretion of ANP from the heart in DOCA- salt rats. The levels of ANP and ANPmRNA in the ventricle of DOCA-salt rats exhibited significant increases, compared with those in control rats, suggesting the induction of ANP gene expression in the ventricle of DOCA-salt hypertensive rats under pre/after overload. Weekly intravenous administrations of monoclonal antibody with high affinity for a-rat ANP significantly augmented the rise in blood pressure of DOCA-salt rats. These results support the hypothesis that the augmented secretion of ANP is one of the defensive mechanisms to counteract high arterial pressure in this model of hypertension.",

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author = "Hiroshi Itoh and Kazuvoa Nakao and Masashi Mukoyama and Hiroshi Arai and Takayuki Yamada and Yoshihiko Saito and Shozo Shiono and Kiminori Hosoda and Gotaro Shirakami and Sinichi Suga and Hiroo Imura",

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AU - Nakao, Kazuvoa

AU - Mukoyama, Masashi

AU - Arai, Hiroshi

AU - Yamada, Takayuki

AU - Saito, Yoshihiko

AU - Shiono, Shozo

AU - Hosoda, Kiminori

AU - Shirakami, Gotaro

AU - Suga, Sinichi

AU - Imura, Hiroo

N1 - Funding Information: This work was supported in part by research grants from the Japa Fproperties,1 a family of cardiac peptides, now istryof Healthand Welfare"Disordersof AdrenalHormone"ReneseMinistryofEducation,ScienceandCulture,theJapaneseMin collectively called atrial natriuretic polypeptides searchCommittee,Japan, 1987, the LifeScienceResearchProjectof (ANPs), have been isolated from rat and human atria in the Institute of Physical and Chemical Research (RIKEN), Japan To several laboratories.2"4 Since then, the heart has at-bolicDisorders,andby researchgrants forcardiovasculardiseases baccoInc.,andtheYamanouchiFoundationfor Researchon Meta tracted attention as a novel endocrine organ involved in ((60A-3) and (62A'-1)) from the Japanese Ministry of Health and body fluid and blood pressure homeostasis.5-7 Several- Welfare. laboratories including ours have reported that plasma MD, PhD,SecondDivision,DepartmentofMedicine,KyotoUniverAddresscorrespondenceand reprintrequests to KazuwaNakao, ANP levels are elevated both in patients with hyperten-sitySchoolofMedicine,54ShogoinKawahara-cho,Sakyo-ku,Kyoto sion,8'9 and in spontaneously hypertensive rats (SHR) 606, Japan. and its substrain, stroke prone SHR (SHR-SP), one of

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KW - Monoclonal antibody

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Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in doca-salt hypertension effects of atrial natriuretic polypeptide monoclonal antibody

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