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  • Title: Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in DOCA-salt hypertension. Effects of atrial natriuretic polypeptide monoclonal antibody.
    Author: Itoh H, Nakao K, Mukoyama M, Arai H, Yamada T, Saito Y, Shiono S, Hosoda K, Shirakami G, Suga S.
    Journal: Am J Hypertens; 1991 Jan; 4(1 Pt 1):39-44. PubMed ID: 1706603.
    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.
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