(Circulation. 1997;95:1214-1221.)
© 1997 American Heart Association, Inc.
Articles |
Potent and Long-Lasting Vasodilatory Effects of Adrenomedullin in Humans
Comparisons Between Normal Subjects and Patients With Chronic Heart Failure
the Second Department of Internal Medicine, Iwate Medical University, Morioka, Iwate, Japan.
Correspondence to Motoyuki Nakamura, MD, Second Department of Internal Medicine, Iwate Medical University, Uchimaru, Morioka, Iwate 020, Japan.
Background Adrenomedullin (ADM) is a recently discovered hypotensive peptide that has been isolated from human pheochromocytoma cells. Observations that ADM is produced from cardiovascular tissue and is found in plasma suggest that it may be important in the regulation of regional vascular resistance.
Methods and Results Limb vascular responses to ADM were examined in 10 healthy subjects and compared with those in 18 patients with chronic heart failure (CHF). The peptide increased forearm blood flow (FBF) from 2.7±0.3 to 11.8±0.9 mL·min-1·100 mL-1 in the control group and from 2.4±0.3 to 6.5±0.7 mL·min-1·100 mL-1 in the CHF group. The ADM-induced FBF increase was significantly impaired in the CHF group (P<.01). After cessation of the infusion, an increased FBF level was sustained for >60 minutes in the control group, whereas in the CHF group the response returned to the baseline in <30 minutes. The ADM infusion increased forearm skin blood flow in both groups (P<.05), whereas the skin blood flow response was impaired in the CHF group (P<.01). The role of nitric oxide in ADM-induced vasorelaxation was also studied in 11 healthy subjects and 6 patients with CHF. FBF and skin blood flow responses during ADM administration were significantly attenuated by NG-monomethyl-L-arginine administration in healthy control subjects (P<.05), whereas both flow responses remained the same in the CHF group.
Conclusions These observations demonstrate that ADM exerts a potent and long-lasting vasodilatory effect on skeletal muscle arteries with involvement of nitric oxide–dependent mechanisms in normal human peripheral vasculature and that these vascular effects are significantly attenuated in patients with CHF, in part because of impaired production of nitric oxide in the forearm resistance vessels.
Key Words: adrenomedullin • endothelium • heart failure • endothelium-derived factors
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|