Intracerebroventricular Atrial Natriuretic Peptide Infusion Augments the Adrenocorticotropin and Angiotensin II Responses to Hemorrhage in Sheep

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Abstract
The central actions of atrial natriuretic peptide (ANP) in rats include inhibition of arginine vasopressin (AVP) release, and less consistently, ACTH suppression and hypotension. To explore any such inhibitory actions on basal and stimulated levels of AVP and ACTH, we have studied the effect of intracerebroventricular (ICV) infusion of ANP on the hemodynamic and hormonal response to acute hemorrhage in conscious sheep. Two groups of 5 sheep received rat ANP(101–126) by ICV infusion (0.5 µg bolus followed by 0.5 µg/h for 3 h, or 5 µg bolus followed by 5 µg/h for 3 h) as well as artificial cerebrospinal fluid control infusions in random order. One hour after the start of the ICV infusion, acute hemorrhage (15 ml/kg BW within 10 min) was performed. Basal levels before hemorrhage of mean arterial pressure (MAP), heart rate and plasma hormones were unaltered by either dose of ICV ANP. After hemorrhage, the fall in MAP and rise in heart rate were similar in each group. However, compared to control infusions the response to hemorrhage of ACTH (433 ± 147 to 2,175 ± 588 vs. control 541 ± 103 to 893 ± 244 ng/1; p < 0.016) and angiotensin II (AII) (18 ± 3 to 94 ± 23 vs. control 18 ± 4 to 58 ± 8 pmol/l; p < 0.001) were significantly greater during high-dose ANP infusion. Although peak AVP levels more than doubled those observed on the control day, the increase did not reach statistical significance (p < 0.1053). Plasma concentrations of cortisol, aldosterone, epinephrine and norepinephrine were not significantly different in control and ANP-treated groups. In conclusion, while central ANP infusion does not alter basal hemodynamic or hormone levels in sheep, the ACTH, AII and AVP responses to hemorrhage are increased. Since the augmented hormone response cannot be attributed to vasodepression, activation by ANP of a central facilitator (such as brain norepinephrine) or suppression of an inhibitor (such as brain natriuretic peptide or opioids) is proposed.