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 alpha-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 alpha-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.
authors.affiliation: Department of Medicine, Kyoto University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Itoh
authors.forename: K
authors.initials: K
authors.lastname: Nakao
authors.forename: M
authors.initials: M
authors.lastname: Mukoyama
authors.forename: H
authors.initials: H
authors.lastname: Arai
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Shiono
authors.forename: K
authors.initials: K
authors.lastname: Hosoda
authors.forename: G
authors.initials: G
authors.lastname: Shirakami
authors.forename: S
authors.initials: S
authors.lastname: Suga
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D001794:Blood Pressure; D015152:Blotting, Northern; D015342:DNA Probes; D003900:Desoxycorticosterone; D015870:Gene Expression; D006325:Heart Atria / Q000737:chemistry; D006352:Heart Ventricles / Q000737:chemistry; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000911:Antibodies, Monoclonal; D015342:DNA Probes; D003900:Desoxycorticosterone; D012313:RNA; D009320:Atrial Natriuretic Factor