Central interaction of the brain atrial natriuretic polypeptide (ANP) system and the brain rennin–angiotensin system in ANP secretion from heart—evidence for possible brain–heart axis

To elucidate the involvement of the brain renin–angiotensin system and the brain atrial natriuretic polypeptide (ANP) system in the regulation of ANP secretion from the heart, the effects of intracerebroventricular administration of angiotensin II and ANP on the plasma ANP level were examined in conscious unrestrained rats. The intracerebroventricular administration of angiotensin II at doses of 100 ng and 1 μg significantly enhanced ANP secretion induced by volume-loading with 3-mL saline infusion (peak values of the plasma ANP level: control, 220 ± 57 pg/mL; 100 ng angiotensin II, 1110 ± 320 pg/mL, p < 0.01; 1 μg angiotensin II, 1055 ± 60 pg/mL, p < 0.01). The intracerebroventricular injection of angiotensin II at the same doses alone had no significant effect on the basal plasma ANP level. The enhancing effect of central angiotensin II on ANP secretion induced by volume-loading was significantly attenuated by pretreatment with the intravenous administration of the V 1 -receptor antagonist of vasopressin or with the intracerebroventricular administration of phentolamine. The intracerebroventricular administration of α-rANP(4–28) (5 μg) had no significant influence on the basal plasma ANP level; however, it significantly attenuated central angiotensin II potentiating effect of volume-loading induced ANP secretion. These results indicate that the brain rennin–angiotensin system regulates ANP secretion via the stimulation of vasopressin secretion and (or) via the activation of the central α-adrenergic neural pathway, and that the brain ANP system interacts with the brain renin–angiotensin system in the central modulation of ANP secretion from the heart. The result further supports the proposed antagonistic relationship between the brain ANP system and the brain renin–angiotensin system in body fluid and blood pressure homeostasis.