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PMID: 2544622 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats.

The Journal of clinical investigation ·Vol. 84 ·No. 1 ·1989-07-00 ·Pages 145-54

Itoh H, Nakao K, Mukoyama M, Yamada T, Hosoda K, Shirakami G, Morii N, Sugawara A, Saito Y, Shiono S

Abstract

To explain the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in the development of hypertension, we examined the effect of chronic, repetitive administrations of MAb raised against alpha-rat ANP in two rat models of hypertension, spontaneously hypertensive rats of the stroke prone substrain (SHR-SP), and deoxycorticosterone acetate (DOCA)-salt rats. Weekly intravenous administrations of MAb with high affinity for alpha-rat ANP, named KY-ANP-II (MAb[KY-ANP-II]), started at the age of 6 wk, significantly augmented the rise in blood pressure of SHR-SP, compared with control SHR-SP treated with another MAb with quite low affinity for alpha-rat ANP, named KY-ANP-I (MAb[KY-ANP-I]), throughout the observation period. The administrations of MAb[KY-ANP-II] had no significant effect on blood pressure of age-matched normotensive Wistar Kyoto rats, compared with those receiving MAb[KY-ANP-I]. Weekly administrations of MAb[KY-ANP-II] also significantly aggravated hypertension in DOCA-salt rats. Blood pressure of DOCA-salt rats treated with MAb[KY-ANP-II] was significantly higher than that of DOCA-salt rats treated with MAb[KY-ANP-I] throughout 8 wk of DOCA and 1% saline administration. The administration of MAb[KY-ANP-II] also significantly attenuated exaggerated diuresis and natriuresis in DOCA-salt rats compared with those treated with MAb[KY-ANP-I]. Elevated plasma cGMP levels of both SHR-SP and DOCA-salt rats were significantly reduced by the administration of MAb[KY-ANP-II]. These results suggest the compensatory role of augmented secretion of ANP in these hypertensive rats and support the concept that augmented secretion of ANP could represent an antihypertensive deterrent mechanism.

MeSH Terms
Animals Antibodies, Monoclonal/immunology Atrial Natriuretic Factor/antagonists & inhibitors,immunology Binding, Competitive Blood Chemical Analysis Blood Pressure Cyclic GMP/antagonists & inhibitors Desoxycorticosterone Diuresis Hypertension/chemically induced,metabolism,pathology Male Potassium/urine Rats Rats, Inbred Strains Rats, Inbred WKY Sodium/urine Sodium Chloride
Chemicals
Antibodies, Monoclonal Desoxycorticosterone Sodium Chloride Atrial Natriuretic Factor Sodium Cyclic GMP Potassium
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Itoh H
Department of Medicine, Kyoto University School of Medicine, Japan.
Nakao K
Mukoyama M
Yamada T
Hosoda K
Shirakami G
Morii N
Sugawara A
Saito Y
Shiono S
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI114134
Published
1989-07-00
Pages
145-54
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC303964
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI114134 PMC Full Text View journal details
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