Is atrial natriuretic peptide-guanosine 3',5' cyclic monophosphate coupling a determinant of urinary sodium excretion in essential hypertension?
OBJECTIVE
(1) To compare urinary guanosine 3',5' cyclic monophosphate (cyclic GMP) excretion between normotensive subjects and essential hypertensive patients; (2) to determine the influence of changes in sodium intake on urinary cyclic GMP excretion in response to the neutral endopeptidase inhibitor candoxatril in essential hypertensives.


METHODS
(1) Twenty-five normotensive subjects and 25 patients with established essential hypertension not on treatment; (2) Single oral dose of candoxatril in eight patients with essential hypertension after equilibration on a low- or high-sodium diet in a placebo-controlled, double-blind, randomized, crossover study.


METHODS
Blood pressure was measured by ultrasound sphygmomanometry. Atrial natriuretic peptide (ANP) and urinary cyclic GMP were measured by radioimmunoassay. Group comparisons were made using unpaired t-tests and two-way analysis of variance.


RESULTS
Plasma ANP was significantly raised in patients with essential hypertension compared with the normotensive group, but there was no difference in urinary cyclic GMP excretion. Plasma ANP increased significantly on the high- compared with low-sodium diet. After candoxatril, there were significant diet-related increases in plasma ANP and urinary sodium excretion up to 6 h after drug administration. There were similar increases in urinary cyclic GMP excretion on both diets, but there were no consistent differences in this excretion between the low- and high-sodium diets.


CONCLUSIONS
These observations not only point to the importance of ANP-cyclic GMP coupling as a determinant of the natriuretic response to endopeptidase inhibition, but also suggest that the excretion of urinary cyclic GMP can be influenced by other factors in addition to circulating ANP.
Sagnella
G A
GA
Department of Medicine, St George's Hospital Medical School, London, UK.
Singer
D R
DR
Markandu
N D
ND
Buckley
M G
MG
MacGregor
G A
GA
D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D006152:Cyclic GMP / Q000652:urine*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology / Q000652:urine*; D007189:Indans / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000502:physiology; D015260:Neprilysin / Q000037:antagonists & inhibitors; D011422:Propionates / Q000494:pharmacology; D012982:Sodium, Dietary / Q000008:administration & dosage*
D007189:Indans; D011422:Propionates; D012982:Sodium, Dietary; D009320:Atrial Natriuretic Factor; C062766:candoxatril; D015260:Neprilysin; D006152:Cyclic GMP