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

Hiroshi Itoh, K. Nakao, M. Mukoyama, T. Yamada, K. Hosoda, G. Shirakami, N. Morii, A. Sugawara, Y. Saito, S. Shiono, H. Arai, I. Yoshida, H. Imura

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

To explain the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in the development of hypertension, we examined of the effect of chronic, repetitive administrations of MAb raised against α-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 administration of MAb with high affinity for α-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 α-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.

Original languageEnglish
Pages (from-to)145-154
Number of pages10
JournalJournal of Clinical Investigation
Volume84
Issue number1
Publication statusPublished - 1989
Externally publishedYes

Fingerprint

Desoxycorticosterone
Acetates
Salts
Monoclonal Antibodies
Hypertension
Peptides
Inbred SHR Rats
Stroke
Blood Pressure
Natriuresis
Inbred WKY Rats

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Itoh, Hiroshi; Nakao, K.; Mukoyama, M.; Yamada, T.; Hosoda, K.; Shirakami, G.; Morii, N.; Sugawara, A.; Saito, Y.; Shiono, S.; Arai, H.; Yoshida, I.; Imura, H.

In: Journal of Clinical Investigation, Vol. 84, No. 1, 1989, p. 145-154.

Research output: Contribution to journalArticle

Itoh, Hiroshi ; Nakao, K. ; Mukoyama, M. ; Yamada, T. ; Hosoda, K. ; Shirakami, G. ; Morii, N. ; Sugawara, A. ; Saito, Y. ; Shiono, S. ; Arai, H. ; Yoshida, I. ; Imura, H. / 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. In: Journal of Clinical Investigation. 1989 ; Vol. 84, No. 1. pp. 145-154.
@article{6d3a3ad2f95d499b9b40c8bf35c487d3,
title = "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",
abstract = "To explain the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in the development of hypertension, we examined of the effect of chronic, repetitive administrations of MAb raised against α-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 administration of MAb with high affinity for α-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 α-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.",
author = "Hiroshi Itoh and K. Nakao and M. Mukoyama and T. Yamada and K. Hosoda and G. Shirakami and N. Morii and A. Sugawara and Y. Saito and S. Shiono and H. Arai and I. Yoshida and H. Imura",
year = "1989",
language = "English",
volume = "84",
pages = "145--154",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

TY - JOUR

T1 - 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

AU - Itoh, Hiroshi

AU - Nakao, K.

AU - Mukoyama, M.

AU - Yamada, T.

AU - Hosoda, K.

AU - Shirakami, G.

AU - Morii, N.

AU - Sugawara, A.

AU - Saito, Y.

AU - Shiono, S.

AU - Arai, H.

AU - Yoshida, I.

AU - Imura, H.

PY - 1989

Y1 - 1989

N2 - To explain the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in the development of hypertension, we examined of the effect of chronic, repetitive administrations of MAb raised against α-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 administration of MAb with high affinity for α-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 α-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.

AB - To explain the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in the development of hypertension, we examined of the effect of chronic, repetitive administrations of MAb raised against α-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 administration of MAb with high affinity for α-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 α-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.

UR - http://www.scopus.com/inward/record.url?scp=0024403211&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024403211&partnerID=8YFLogxK

M3 - Article

VL - 84

SP - 145

EP - 154

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 1

ER -