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 established. The objectives of this study were to determine whether untreated essential hypertensive patients are more sensitive to the antinatriuretic action of insulin and more resistant to the counteracting natriuretic effect of atrial natriuretic peptide in contrast to age- and sex-matched normotensive control subjects. Urinary sodium excretion was measured at baseline, during hyperinsulinemic euglycemic clamp, and during coadministration of insulin and atrial natriuretic peptide. Baseline urinary sodium excretion was not significantly different in the normotensive subjects (415 +/- 47 mumol/min, n = 12) and hypertensive patients (381 +/- 18 mumol/min, n = 10); with the institution of insulin infusion, there was a similar and significant decline from baseline (P < .001) to 289 +/- 35 mumol/min in normotensive subjects and 235 +/- 17 mumol/min in hypertensive patients. Atrial natriuretic peptide was able to oppose the antinatriuretic action of insulin in normotensive subjects, increasing urinary sodium excretion significantly to a mean level of 352 +/- 31 mumol/min (P < .05), which did not differ significantly from baseline. In the hypertensive group, atrial natriuretic peptide infusion had no effect on urinary sodium excretion (238 +/- 18 mumol/min), and the difference from baseline remained highly significant (P < .001). The hypertensive patients were significantly less insulin sensitive than their normotensive counterparts, as reflected by a lower glucose utilization rate and higher mean baseline plasma insulin level (P < .05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)
Abouchacra
S
S
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Baines
A D
AD
Zinman
B
B
Skorecki
K L
KL
Logan
A G
AG
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D015309:Glucose Clamp Technique; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007333:Insulin Resistance; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D012079:Renal Circulation; D012964:Sodium / Q000378:metabolism
D007328:Insulin; D009320:Atrial Natriuretic Factor; D012964:Sodium