Therapeutic potential of atrial natriuretic peptide administration on peripheral arterial diseases.
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.
Park
Kwijun
K
Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Tokyo, Japan. hiito@kuhp.kyoto-u.ac.jp
Itoh
Hiroshi
H
Yamahara
Kenichi
K
Sone
Masakatsu
M
Miyashita
Kazutoshi
K
Oyamada
Naofumi
N
Sawada
Naoya
N
Taura
Daisuke
D
Inuzuka
Megumi
M
Sonoyama
Takuhiro
T
Tsujimoto
Hirokazu
H
Fukunaga
Yasutomo
Y
Tamura
Naohisa
N
Nakao
Kazuwa
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001162:Arteriosclerosis Obliterans / Q000188:drug therapy / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D016523:Foot Ulcer / Q000188:drug therapy / Q000503:physiopathology; D005734:Gangrene / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016491:Peripheral Vascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects*; D013919:Thromboangiitis Obliterans / Q000188:drug therapy / Q000503:physiopathology; D016896:Treatment Outcome
C472955:NPPA protein, human; D009320:Atrial Natriuretic Factor