title: Potentiation of C-type natriuretic peptide with ultrasound and microbubbles to prevent neointimal formation after vascular injury in rats.
abstract: OBJECTIVE
  Long-term intravenous infusion of high-dose C-type natriuretic peptide (CNP) is known to prevent neointimal formation after vascular injury. Ultrasound (US) irradiation during microbubbles (MBs) infusion (US/MBs) has been used for local delivery of bioactive agents. We examined whether short-term infusion of CNP could also inhibit neointimal development and whether combined US/MBs treatment at the beginning of the CNP infusion could enhance its effect.
  
  
  METHODS
  In the rat carotid artery-balloon injury model, the intima/media area (I/M) ratio 14 days after injury was compared among various short-term post-injury treatments. For combined US/MBs, a commercial echocardiograph (1.8 MHz, mechanical index 1.0) and albumin-coated octafluoropropane gas MBs were used.
  
  
  RESULTS
  Infusion of high-dose CNP (1.0 microg/kg/min) immediately after injury for only 24 h successfully reduced the I/M ratio (0.18+/-0.05) to 18% of the ratio in control rats (1.00+/-0.13) that underwent only balloon injury. Although low-dose CNP (0.1 microg/kg/min for 24 h) alone was not effective in reducing the I/M ratio (0.83+/-0.18), combined US/MBs treatment for the first 80 min of the infusion markedly reduced the I/M ratio (0.17+/-0.07), which persisted until 28 days after injury (0.16+/-0.04).
  
  
  CONCLUSIONS
  The effects of CNP on the events occurring early after arterial injury may be important in preventing subsequent neointimal development. Thus, intravenous infusion of CNP with US/MBs at its initiation may provide a clinically feasible anti-restenosis therapy applicable immediately after vascular interventions.
authors.affiliation: Second Department of Internal Medicine, Kagawa Medical University, Kita-gun, Kagawa, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Koji
authors.initials: K
authors.lastname: Ohmori
authors.forename: Isao
authors.initials: I
authors.lastname: Kondo
authors.forename: Akira
authors.initials: A
authors.lastname: Oshita
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Takagi
authors.forename: Katsufumi
authors.initials: K
authors.lastname: Mizushige
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D017115:Catheter Ablation; D003131:Combined Modality Therapy; D006152:Cyclic GMP / Q000378:metabolism; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D014464:Ultrasonic Therapy; D014463:Ultrasonography
chemical_list: D020098:Natriuretic Peptide, C-Type; D006152:Cyclic GMP