Effects of physiological increments in human alpha-atrial natriuretic peptide and human brain natriuretic peptide in normal male subjects.
1. Brain natriuretic peptide, closely related to atrial natriuretic peptide in structure, may be an important circulating hormone. Its physiological role is unclear. First, we studied the effects of incremental infusions of brain natriuretic peptide in six healthy men on plasma brain natriuretic peptide levels and the pharmacokinetics of brain natriuretic peptide. Synthetic human brain natriuretic peptide-32 was infused intravenously, at an initial rate of 0.4 pmol min-1 kg-1, doubling every 15 min until the dose rate reached 6.4 pmol min-1 kg-1, at which rate the infusion was maintained for 30 min. 2. The brain natriuretic peptide infusion raised the brain natriuretic peptide-like immunoreactivity from 1.4 +/- 0.5 pmol/l to 21.4 +/- 7.6 pmol/l. Brain natriuretic peptide-like immunoreactivity after the end of infusion was consistent with a bi-exponential decay, with half-lives of 2.1 min and 37 min. 3. Next, we studied the effects of low-dose infusion of brain natriuretic peptide to mimic physiological increments in the circulating levels in comparison with atrial natriuretic peptide. Six dehydrated male subjects received intravenous infusions of atrial natriuretic peptide and brain natriuretic peptide, separately and in combination, in a randomized double-blind, placebo-controlled, four-part cross-over design. Atrial natriuretic peptide and brain natriuretic peptide were given at the rate of 0.75 and 0.4 pmol min-1 kg-1, respectively, for 3 h. The control infusion consisted of the vehicle. 4. Analysis of variance showed that atrial natriuretic peptide and atrial natriuretic peptide plus brain natriuretic peptide, but not brain natriuretic peptide alone, increased urinary flow and decreased urinary osmolality significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Cheung
B M
BM
Department of Medicine, Addenbrooke's Hospital, Cambridge, U.K.
Dickerson
J E
JE
Ashby
M J
MJ
Brown
M J
MJ
Brown
J
J
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D006207:Half-Life; D006801:Humans; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D009994:Osmolar Concentration; D014556:Urine
D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor