Growth hormone-releasing peptide (GHRP, SK&F 110679) is a hexapeptide (His-DTrp-Ala-Trp-DPhe-LysNH2) that selectively stimulates the release of growth hormone (GH) but not other pituitary hormones in vitro and in vivo in a variety of animal species. GHRP was administered to 17 normal men at doses of from 0.05 to 2.5 micrograms/kg as a 30 min intravenous infusion. Eight of the men were infused with saline as a control. Serum GH increased consistently at doses of 0.25 microgram/kg and above during the infusion of the peptide, peaked at 45 min and then decreased to baseline values by 210 min. The mean peak serum GH concentrations (+/- SE) in response to GHRP infusion were 17.8 +/- 6.1 micrograms/L at a dose of 0.25 microgram/kg (n = 4, p = .03 vs saline), 38.3 +/- 9.2 micrograms/L at 0.5 microgram/kg (n = 4, p = .04 vs saline) and 63.0 +/- 5.4 micrograms/L at 1.0 microgram/kg (n = 4, p = .002 vs saline). Serum LH, FSH, TSH and ACTH were unaffected by GHRP administration. GHRP was safe and well-tolerated in all men. GHRP infusion resulted in a dramatic, selective and dose-dependent increase in serum GH concentrations.
Fenoldopam, a dopamine agonist, was evaluated in renal clearance studies during water diuresis after oral doses of 25, 50, and 100 mg. After the 100-mg dose there was an increase in urine flow rate, paraaminohippurate clearance, free water clearance, and an increase in the fractional excretion of sodium, calcium, and uric acid. These effects were evident within the first hour, peaked during the second hour, and lasted about 3 hr. Doses of 50 and 25 mg induced smaller increases. There was no significant change in inulin clearance at any dose. To elucidate the mechanism of action, the studies were repeated after treatment with a dopamine-receptor antagonist (metoclopramide). Metoclopramide greatly diminished the renal effects of fenoldopam. These findings indicate that fenoldopam is an active renal vasodilator in man and increases urine volume, free water clearance, and fractional excretion of sodium by stimulation of renal dopamine receptors.
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