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Therapeutic potential of atrial natriuretic peptide administration on peripheral arterial diseases.
- Source :
-
Endocrinology [Endocrinology] 2008 Feb; Vol. 149 (2), pp. 483-91. Date of Electronic Publication: 2007 Nov 08. - Publication Year :
- 2008
-
Abstract
- Peripheral arterial diseases are caused by arterial sclerosis and impaired collateral vessel formation, which are exacerbated by diabetes, often leading to leg amputation. We have reported that an activation of the natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway accelerated vascular regeneration and blood flow recovery in murine legs, for which ischemia had been induced by a femoral arterial ligation as a model for peripheral arterial diseases. In this study, ip injection of carperitide, a human recombinant atrial natriuretic peptide, accelerated blood flow recovery with increasing capillary density in ischemic legs not only in nondiabetic mice but also in mice kept upon streptozotocin-induced hyperglycemia for 16 wk, which significantly impaired the blood flow recovery compared with nondiabetic mice. Based on these findings, we tried to apply the administration of carperitide to the treatment of peripheral arterial diseases. The study group comprised a continuous series of 13 patients with peripheral arterial diseases (Fontaine's classification I, one; II, five; III, two; and IV, five), for whom conventional therapies had not accomplished appreciable results. Carperitide was administrated continuously and intravenously for 2 wk to Fontaine's class I-III patients and for 4 weeks to class IV patients. The dose was gradually increased to the maximum, with the patient's systolic blood pressure being kept above 100 mm Hg. Carperitide administration improved the ankle-brachial pressure index, intermittent claudication, rest pain, and ulcers. In conclusion, this study showed a therapeutic potential of carperitide to treat peripheral arterial diseases refractory to conventional therapies.
- Subjects :
- Adult
Aged
Aged, 80 and over
Animals
Arteriosclerosis Obliterans drug therapy
Arteriosclerosis Obliterans physiopathology
Blood Pressure drug effects
Diabetes Mellitus, Experimental complications
Diabetic Angiopathies drug therapy
Diabetic Angiopathies physiopathology
Female
Foot Ulcer drug therapy
Foot Ulcer physiopathology
Gangrene drug therapy
Gangrene physiopathology
Humans
Infusions, Intravenous
Male
Mice
Mice, Inbred C57BL
Middle Aged
Peripheral Vascular Diseases physiopathology
Thromboangiitis Obliterans drug therapy
Thromboangiitis Obliterans physiopathology
Treatment Outcome
Atrial Natriuretic Factor administration & dosage
Neovascularization, Physiologic drug effects
Peripheral Vascular Diseases drug therapy
Regional Blood Flow drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0013-7227
- Volume :
- 149
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 17991722
- Full Text :
- https://doi.org/10.1210/en.2007-1094