Role of prostaglandins and renal nerves in the renal actions of
adrenomedullin.
Jougasaki, Michihisa, Lawrence L. Aarhus, Denise M. Heublein, Sharon
M. Sandberg, and John C. Burnett.
Cardiorenal Research Laboratory, Division of Cardiovascular
Diseases, Mayo Clinic and Foundation, Rochester MN 55905
APStracts 3:0210F, 1996.
Adrenomedullin (ADM), originally discovered in human pheochromocytoma,
is also of renal cell origin and has natriuretic and diuretic
actions. The present study was designed to investigate the role of
prostaglandins and renal nerves in the renal hemodynamic and
natriuretic actions of ADM. ADM was administered intrarenally (1, 5
and 25 ng/kg/min) with and without prostaglandin inhibition
(meclofenamate, 5 mg/kg intravenous bolus) in anesthetized normal
mongrel dogs (n=5, each). To elucidate the role of renal nerves, ADM
was administered intrarenally to the denervated kidney in 5 dogs. ADM
mediated a natriuretic action via increases in glomerular filtration
rate and decreases in distal tubular sodium reabsorption which was
attenuated by renal denervation and completely abolished by
prostaglandin inhibition. The renal vasodilatation induced by ADM was
attenuated by meclofenamate as well as by renal denervation, although
not significantly. Additionally, renal nerves mediated hemodynamic
effects of hypertension that were produced by intrarenal infusion of
ADM. This study establishes an important mechanistic role for renal
prostaglandins as a mediator of ADM-mediated natriuresis at the level
of the glomerulus and terminal nephron.
Received 16 January 1996; accepted in final form 28 October 1996.
APS Manuscript Number F8-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996