N. Yokota et al., ATRIAL-NATRIURETIC-FACTOR SIGNIFICANTLY CONTRIBUTES TO THE MINERALOCORTICOID ESCAPE PHENOMENON - EVIDENCE FOR A GUANYLATE CYCLASE-MEDIATED PATHWAY, The Journal of clinical investigation, 94(5), 1994, pp. 1938-1946
The mechanism underlying the mineralocorticoid escape phenomenon remai
ns unknown. To assess the possible contribution of natriuretic peptide
s to mineralocorticoid escape, rats were injected with 5 mg deoxycorti
costerone acetate for 3 d. Plasma atrial natriuretic factor (ANF) rose
to twice basal levels and atrial ANF content decreased significantly
by 24 h of treatment. This coincided with renal escape and with a sign
ificant increase in urinary cGMP excretion. Plasma ANF remained elevat
ed and atrial ANF content continued to decline by 48 and 72 h while at
rial ANF mRNA levels increased significantly only at 72 h. Plasma brai
n natriuretic peptide did not increase during escape although atrial b
rain natriuretic peptide mRNA levels increased significantly. Chronica
lly administered HS-142-1 (HS), a specific antagonist of the guanylate
cyclase-coupled natriuretic peptide receptors, significantly and dose
-dependently impaired the escape phenomenon. The highest dose of HS co
mpletely suppressed the increase in urinary cGMP. Despite the continue
d suppression, partial escape was observed by the end of the observati
on period. HS alone influenced neither plasma nor tissue or urine para
meters. These findings show that despite activation of atrial ANF, blo
ckade of the guanylate cyclase-coupled natriuretic peptide receptors i
mpairs the ability of the kidney to escape the Na+ retaining effect of
excess mineralocorticoid in a dose-dependent fashion. Later-acting, u
nknown mechanisms eventually come into play to mediate the escape phen
omenon through a guanylate cyclase-independent pathway. Therefore, ANF
of cardiac origin appears to be a major factor initiating mineralocor
ticoid escape through a guanylate cyclase-dependent pathway.