The antinatriuretic action of biosynthetic human growth hormone in man involves activation of the renin-angiotensin system

Abstract

Previous studies using human pituitary extracts have not resolved whether the sodium retaining effects of human growth hormone (hGH) are mediated in part by increased aldosterone secretion. We have studied the effects of an authentic biosynthetic GH (bio-hGH) preparation on sodium metabolism and on the activity of the renin-angiotensin system. Six young men were administered this preparation at 0.2 U/kg/d subcutaneously for five consecutive days. Twenty-four-hour urine collections were obtained for measurement of sodium excretion and osmolality and blood collected for quantitating changes in sodium, osmolality, plasma renin activity (PRA), aldosterone, and arginine vasopressin (AVP) concentrations. Bio-hGH administration resulted in a fall in 24-hour urinary sodium excretion (197 ± 38 to 42 ± 20 mmol, mean ± SD, P < .005), a reduction in urine volume (1,652 ± 182 to 848 ± 348 mL, P < .05) but not osmolality. PRA increased significantly from 1,118 ± 73 to 3,608 ± 1,841 fmol angiotensin 1 L/s ( P < .005), which was associated with a sevenfold increase in plasma aldosterone concentration (52 ± 12 to 402 ± 99 pg/mL, P < .001). Plasma osmolality and AVP concentrations did not change significantly. The results show that Bio-GH-induced retention of sodium involves the activation of the renin-angiotensin system. This mechanism may explain in part the occurrence of plasma volume expansion and hypertension in acromegaly and suggests a risk of fluid retention and possibly hypertension in subjects receiving supraphysiological doses of bio-hGH for treatment of short stature.