HEMODYNAMIC, HORMONAL, AND RENAL EFFECTS OF INTRACEREBROVENTRICULAR ADRENOMEDULLIN IN CONSCIOUS SHEEP

Adrenomedullin, the recently described vasodilator that exhibits poten t 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 th e integrative hemodynamic, renal, and hormonal effects of intracerebro ventricular (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 i nfusion resulted in sheep drinking 2617 +/- 583 mi in the 90-min perio d following reintroduction of water. On the adrenomedullin day, drinki ng was halved to 1392 +/- 361 mi (P < 0.05). Adrenomedullin had no sig nificant effect on urinary volume and sodium excretion. Plasma adrenom edullin levels remained unchanged during control infusions but were el evated by the end of ICV adrenomedullin infusions (P < 0.001). Plasma ANP levels were also increased approximately 50% (P < 0.05). Plasma le vels of both ACTH and cortisol were also increased 3- to 4-fold in res ponse to ICV adrenomedullin (P < 0.05). There was no significant diffe rence in arterial pressure, heart rate, or cardiac output between stud y days. In conclusion, adrenomedullin within the central nervous syste m may have at least two roles: modulation of the hypothalamo-pituitary -adrenal axis and protection against fluid overload.