Document Detail


Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study.
MedLine Citation:
PMID:  8989240     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adrenomedullin has been proposed to be a circulating hormone regulating systemic and pulmonary blood pressure. A potential therapeutic role in the management of pulmonary hypertension has been suggested based on animal studies, but the pharmacokinetics and pharmacodynamics in human subjects have not been studied. We have infused adrenomedullin into volunteers at 3.2 pmol/kg.min, which more than quadrupled (52 pmol/L) normal circulating concentrations. At this dose no change in heart rate or blood pressure was noted. When infused at 13.4 pmol/kg.min to achieve a concentration over 40 times normal circulating levels (448 pmol/L), there was a significant fall in diastolic blood pressure from 69 +/- 2 to 53 +/- 2 mm Hg and a significant increase in pulse rate from 57 +/- 3 to 95 +/- 4 beats/min. Circulating PRL concentrations rose from 197 +/- 46 to 372 +/- 64 IU/L (mean +/- SEM; P < 0.01). No effect was seen on ACTH, TSH, FSH, LH, or cortisol. When the infusion was discontinued, baseline pulse and blood pressure were reestablished after 20 min. Adrenomedullin has a MCR of 27.4 +/- 3.6 mL/kg.min, with a circulating half life of 22 +/- 1.6 min and an apparent volume of distribution of 880 +/- 150 mL/kg. Column chromatography of plasma taken during infusion and decay of adrenomedullin showed no evidence of the production of additional molecular forms. These results are consistent with a peptide that is markedly tissue bound. Plasma adrenomedullin concentrations were increased in patients with renal impairment (14.1 +/- 0.9 pmol/L) compared to those in healthy volunteers (8.1 +/- 0.7 pmol/L), with a good correlation (r = 0.86) between circulating adrenomedullin and plasma creatinine. The circulating concentration of adrenomedullin necessary to affect blood pressure greatly exceeds that observed in healthy volunteers and in patients with a range of pathological conditions. Thus, adrenomedullin may be a paracrine regulator of vascular smooth muscle in humans.
Authors:
K Meeran; D O'Shea; P D Upton; C J Small; M A Ghatei; P H Byfield; S R Bloom
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  82     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-01-30     Completed Date:  1997-01-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  95-100     Citation Subset:  AIM; IM    
Affiliation:
Division of Endocrinology and Metabolism, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Adrenomedullin
Adult
Blood Pressure / drug effects*
Half-Life
Humans
Infusions, Intravenous
Male
Metabolic Clearance Rate
Peptides / administration & dosage*,  blood,  pharmacokinetics*
Prolactin / blood*
Pulse / drug effects
Chemical
Reg. No./Substance:
0/Peptides; 148498-78-6/Adrenomedullin; 9002-62-4/Prolactin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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