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Hemodynamic, Hormonal, and Renal Effects of Intracerebroventricular Adrenomedullin in Conscious Sheep¹

Department of Medicine, Christchurch School of Medicine, Christchurch 8001, New Zealand; Department of Medicine, School of Medicine, Developmental Biology and Cancer Research Group, School of Biological Sciences, University of Auckland, Auckland 1, New Zealand, and Department of Medicine, Tulane University, New Orleans, Louisiana 70112

Address all correspondence and requests for reprints to: Dr. C. J. Charles, Department of Medicine, Christchurch School of Medicine, P.O. Box 4345, Christchurch, New Zealand. E-mail: endolab5{at}chmeds.ac.nz

Adrenomedullin, the recently described vasodilator that exhibits potent hypotensive actions when administered systemically, is also found in the central nervous system, suggesting a role for adrenomedullin as a neurohormone. However, only a limited number of studies have examined the central effects of adrenomedullin. Therefore, we have examined the integrative hemodynamic, renal, and hormonal effects of intracerebroventricular (ICV) adrenomedullin in conscious sheep. Eight surgically prepared sheep received ICV infusions of adrenomedullin at two doses (2 ng/kg·min followed immediately by 20 ng/kg·min each for 90 min) in a vehicle-controlled study. Water deprivation for 48 h before control infusion resulted in sheep drinking 2617 ± 583 ml in the 90-min period following reintroduction of water. On the adrenomedullin day, drinking was halved to 1392 ± 361 ml (P < 0.05). Adrenomedullin had no significant effect on urinary volume and sodium excretion. Plasma adrenomedullin levels remained unchanged during control infusions but were elevated by the end of ICV adrenomedullin infusions (P < 0.001). Plasma ANP levels were also increased approximately 50% (P < 0.05). Plasma levels of both ACTH and cortisol were also increased 3- to 4-fold in response to ICV adrenomedullin (P < 0.05). There was no significant difference in arterial pressure, heart rate, or cardiac output between study days. In conclusion, adrenomedullin within the central nervous system may have at least two roles: modulation of the hypothalamo-pituitary-adrenal axis and protection against fluid overload.

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