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

H. 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

研究成果: Article査読

51 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)145-154
ページ数10
ジャーナルJournal of Clinical Investigation
84
1
DOI
出版ステータスPublished - 1989
外部発表はい

ASJC Scopus subject areas

  • 医学(全般)

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