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

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 a-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 a-rat ANP, named KY-ANP-II (MAb[KY-ANP-IIJ), 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 a-rat ANP, named KY-ANP-I (MAb[KY-ANP-IJ), throughout the observation period. The administrations of MAblKY-ANP-IIj had no significant effect on blood pressure of age-matched normotensive Wistar Kyoto rats, compared with those receiving MAbIKY-ANP-Ij. Weekly administrations of MAbIKY-ANP-III also significantly aggravated hypertension in DOCA-salt rats. Blood pressure of DOCA-salt rats treated with MAb[KY-ANP-IIJ was significantly higher than that of DOCA-salt rats treated with MAb[KY-ANP-IJ throughout 8 wk of DOCA and 1% saline administration. The administration of MAb[KY-ANP-IIJ also significantly attenuated exaggerated diuresis and natriuresis in DOCA-salt rats compared with those treated with MAbIKY-ANP-II. Elevated plasma cGMP levels of both SHR-SP and DOCA-salt rats were significantly reduced by the administration of MAbIKYANP-II1. These results suggest the compensatory role of augmented secretion of ANP in these hypertensive rats and support the concept that augmented secretion ofANP could represent an antihypertensive deterrent mechanism.