Potentiation of C-type natriuretic peptide with ultrasound and microbubbles to prevent neointimal formation after vascular injury in rats.
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.
Takeuchi
Hiroto
H
Second Department of Internal Medicine, Kagawa Medical University, Kita-gun, Kagawa, Japan.
Ohmori
Koji
K
Kondo
Isao
I
Oshita
Akira
A
Shinomiya
Kaori
K
Yu
Yang
Y
Takagi
Yuichiro
Y
Mizushige
Katsufumi
K
Kangawa
Kenji
K
Kohno
Masakazu
M
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
D020098:Natriuretic Peptide, C-Type; D006152:Cyclic GMP