INSULIN BLUNTS THE NATRIURETIC ACTION OF ATRIAL-NATRIURETIC-PEPTIDE IN HYPERTENSION

Hyperinsulinemia and insulin resistance are implicated in the etiology of hypertension, but the mechanisms involved have not been establishe d. The objectives of this study were to determine whether untreated es sential hypertensive patients are more sensitive to the antinatriureti c action of insulin and more resistant to the counteracting natriureti c effect of atrial natriuretic peptide in contrast to age- and sex-mat ched normotensive control subjects. Urinary sodium excretion was measu red at baseline, during hyperinsulinemic euglycemic clamp, and during coadministration of insulin and atrial natriuretic peptide. Baseline u rinary sodium excretion was not significantly different in the normote nsive subjects (415+/-47 mu mol/min, n = 12) and hypertensive patients (381+/-18 mu mol/min, n = 10); with the institution of insulin infusi on, there was a similar and significant decline from baseline (P<.001) to 289+/-35 mu mol/min in normotensive subjects and 235+/-17 mu mol/m in in hypertensive patients. Atrial natriuretic peptide was able to op pose the antinatriuretic action of insulin in normotensive subjects, i ncreasing urinary sodium excretion significantly to a mean level of 35 2+/-31 mu mol/min (P<.05), which did not differ significantly from bas eline. In the hypertensive group, atrial natriuretic peptide infusion had no effect on urinary sodium excretion (238+/-18 mu mol/min), and t he difference from baseline remained highly significant (P<.001). The hypertensive patients were significantly less insulin sensitive than t heir normotensive counterparts, as reflected by a lower glucose utiliz ation rate and higher mean baseline plasma insulin level (P<.05 for ea ch). We conclude that resistance to the natriuretic action of atrial n atriuretic peptide may be a pathogenetic link between insulin resistan ce and hypertension.