Atrial natriuretic peptide preserves endothelial function during intimal hyperplasia.
BACKGROUND
Atrial and C-type natriuretic peptides (ANP and CNP), acting through different receptors, have antiproliferative effects in vitro. Beneficial effects of CNP in vivo on early atherosclerosis have been described, but it is not known if ANP is antiproliferative in vivo. In the present study, the effects of chronic in vivo ANP were tested and compared with CNP on endothelial dysfunction and intimal thickening caused by peri-arterial collars.


METHODS
Non-occlusive collars were placed bilaterally around the common carotid arteries of rabbits. One collar was filled with saline vehicle. The contralateral collar was filled with ANP or CNP (1 or 10 microM, n = 5-7) with slow replacement of peptide via mini-pump (1 or 10 fmol/h).


RESULTS
After 7 days, endothelium-dependent vasorelaxation in saline-collared arteries was 33 +/- 3% of maximum [averaged over 0.03-1 muM acetylcholine (ACh)] compared to 64 +/- 2% in normal (uncollared) arteries (p < 0.05, n = 23). In vivo ANP restored the ACh relaxation to normal (e.g., 57 +/- 6%, 1 microM ANP), similar to effects seen with CNP in vivo. Endothelium-independent vasorelaxation of collared-vessels was not altered by either peptide. Intimal hyperplasia induced by the collars was not prevented by peri-arterial natriuretic peptides. In additional rabbits (n = 6), CNP (100 pmol/h) given directly into the lumen of collared carotid arteries for 7 days reduced neointima formation by 16 +/- 5% (p < 0.05), whereas ANP given intraluminally (100 pmol/h; n = 6) did not.


CONCLUSIONS
The more potent actions of CNP on vascular smooth muscle cell migration and proliferation (established in vitro) may explain differences between the peptides on intimal hyperplasia in vivo. The major hallmark of atherosclerosis and restenosis, endothelial dysfunction, was prevented by chronic, peri-arterial administration of ANP or CNP.
Barber
Melissa N
MN
Howard Florey Institute, University of Melbourne, Melbourne, Vic. 3010, Australia.
Gaspari
Tracey A
TA
Kairuz
Evette M
EM
Dusting
Gregory J
GJ
Woods
Robyn L
RL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D006965:Hyperplasia; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits; D017539:Tunica Intima / Q000473:pathology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D000109:Acetylcholine