C. Sala et al., Blunted vascular and renal effects of exogenous atrial natriuretic peptidein patients with Gushing's disease, J CLIN END, 86(5), 2001, pp. 1957-1961
The role of atrial natriuretic peptide (ANP) in glucocorticoid hypertension
is still controversial, as glucocorticoids enhance the secretion of ANP in
vivo, but reduce its biological activity in vitro. In isolated cells, for
example, the cGMP response to ANP is suppressed by dexamethasone. We tested
the in vivo relevance of this observation by comparing the cGMP, endocrine
, and renal responses to exogenous ANP in patients with Gushing's disease (
CD; n = 10) and in a matched group of essential hypertensives (EH; n = 8) a
nd normotensive controls (N; n = 4). alpha -human-ANP was infused at 0.01 m
ug/kg/min for 120 min with a 30-min recovery period; hormonal and arterial
pressure measurements were performed at 30-min intervals, and renal paramet
ers were measured at baseline and after infusion.
There was a 4-fold increase in plasma ANP in all groups, but the increments
in plasma cGMP were about 50% lower in CD than in N and EH; urinary cGMP w
as similarly lower in GD (247 +/- 61 vs. 529 +/- 146 and 384 +/- 54 nmol/15
0 min, respectively). This was associated with a reduced peak increase in h
ematocrit in GD (+2.6 +/- 0.9%) compared, with N (+6.6 +/- 0.9%) and EH (+7
.1 +/- 0.7%; P < 0.05 CD us. both); the diuretic and natriuretic effects of
ANP were also lower in CD than in EH with very similar systemic pressure l
evels (382 <plus/minus> 63 vs. 848 +/- 130 mL/150 min, and 61 + 14 vs. 113
+/- 14 mmol/150 min, respectively; P < 0.05 for both).
The increments in plasma and urinary cGMP in response to physiological dose
s of ANP are thus blunted in CD patients compared with those in M and EH. T
his biochemical defect is associated with reduced capillary permeability an
d a lesser diuretic and natriuretic effect. These data are compatible with
an impairment of the biological activity of ANP in glucocorticoid hypertens
ion in humans.