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Research Article Free access | 10.1172/JCI114134

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, and S Shiono

Department of Medicine, Kyoto University School of Medicine, Japan.

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Department of Medicine, Kyoto University School of Medicine, Japan.

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Department of Medicine, Kyoto University School of Medicine, Japan.

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Department of Medicine, Kyoto University School of Medicine, Japan.

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Department of Medicine, Kyoto University School of Medicine, Japan.

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Department of Medicine, Kyoto University School of Medicine, Japan.

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Department of Medicine, Kyoto University School of Medicine, Japan.

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Department of Medicine, Kyoto University School of Medicine, Japan.

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Department of Medicine, Kyoto University School of Medicine, Japan.

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Department of Medicine, Kyoto University School of Medicine, Japan.

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Published July 1, 1989 - More info

Published in Volume 84, Issue 1 on July 1, 1989
J Clin Invest. 1989;84(1):145–154. https://doi.org/10.1172/JCI114134.
© 1989 The American Society for Clinical Investigation
Published July 1, 1989 - Version history
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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.

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