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Hormone and Hemodynamic Responses to Atrial Natriuretic Peptide in Conscious Sheep and Effect of Hemorrhage^*

Princess Margaret Hospital Christchurch 2, New Zealand

Address requests for reprints to: Dr. Vicky A. Cameron, Department of Endocrinology, Princess Margaret Hospital, Cashmere Road, Christchurch 2, New Zealand.

Abstract

The effect of rat atrial natriuretic peptide (ANP) on basal hemodynamic and hormonal function and on the response to acute hemorrhage was studied in eight conscious sheep. ANP infusions (3 µg/kg BW bolus, followed by 50 ng/kg-min for 70 min) increased plasma immunoreactive ANP levels from less than 12 pmol/liter to steady state levels of 523 ± 20 pmol/ liter, reduced arterial pressure by 14% (P < 0.002), increased heart rate by 26% (P < 0.06), and increased plasma norepinephrine levels (P < 0.015) compared to control values. These changes were associated with a significant increase in plasma cortisol (P < 0.05) and smaller increases in plasma ACTH and arginine vasopressin (AVP), but plasma angiotensin II (All) and aldosterone were unaffected. When hemorrhage (15 ml/kg BW over 10 min) was performed during ANP or control infusions, hypotension was greater (P < 0.0004) during ANP treatment and the responses of plasma ACTH, AVP, catecholamines, and All were enhanced compared with those to control hemorrhage. Plasma immunoreactive ANP during ANP infusions was significantly higher after hemorrhage (mean, 833 ± 46; P < 0.003), but the disappearance rate after the termination of ANP infusion was the same (3.1 min) with or without hemorrhage.

These studies show that ANP infusions, achieving plasma levels observed in pathological states such as congestive heart failure, inhibit the expected responses of plasma All and aldosterone to mild acute hypotension, but do not inhibit the responses of plasma AVP, ACTH, All, and aldosterone associated with acute moderate hemorrhage in conscious sheep. (Endocrinology 122: 407–414,1988)

Footnotes

^* This work was supported by grants from the Medical Research Council and the National Heart Foundation of New Zealand.

Received March 27, 1987.