Vascular actions of brain natriuretic peptide: modulation by atherosclerosis and neutral endopeptidase inhibition.

Abstract

OBJECTIVES:

We sought to define the vascular actions of the cardiac hormone brain natriuretic peptide (BNP) on cellular proliferation and cyclic guanosine monophosphate (cGMP) in human aortic vascular smooth muscle cells (HAVSMCs). Secondly, we investigated BNP and acetylcholine (ACh) vasorelaxations in aortic rings from normal and atherosclerotic rabbits in the presence and absence of long-term oral inhibition of neutral endopeptidase (NEP).

BACKGROUND:

The vascular actions of BNP are not well defined, despite the presence of its receptor in vascular smooth muscle and the upregulation of NEP, the ectoenzyme that degrades BNP, in the vascular wall in atherosclerosis.

METHODS:

HAVSMCs stimulated with fetal calf serum (FCS) were pulsed with bromodeoxyuridine (BrdU) with and without BNP. The HAVSMCs were incubated in the presence and absence of BNP to assess cGMP. Vasorelaxations to BNP and ACh were assessed in rings in normal and atherosclerotic rabbits in the presence and absence of long-term oral inhibition of NEP, together with assessment of atheroma formation.

RESULTS:

FCS-stimulated BrdU uptake in HAVSMCs was suppressed with BNP. BNP potentiated cGMP in HAVSMCs. BNP resulted in potent vasorelaxation in normal isolated aortic rings, which were impaired in atherosclerotic versus normal rabbits and preserved with NEP inhibition, which also decreased atheroma formation. Relaxations to ACh, which were also impaired in atherosclerosis, were preserved with inhibition of NEP.

CONCLUSIONS:

We conclude that BNP potently inhibits vascular smooth muscle cell proliferation and potentiates the generation of cGMP. BNP potently relaxes the normal rabbit aorta, and this response is impaired in atherosclerosis but preserved with inhibition of NEP, together with a reduction in atheroma formation and preservation of relaxations to ACh.

• Authors: J A Schirger, J A Grantham, I J Kullo, M Jougasaki, P W Wennberg, H H Chen, O Lisy, V Miller, R D Simari, J C Burnett Jr
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 35 Issue 3 Pg. 796-801 (Mar 01 2000) ISSN: 0735-1097 [Print] United States
• PMID: 10716485 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Vasoconstrictor Agents
• Vasodilator Agents
• Natriuretic Peptide, Brain
• Phenylephrine
• Neprilysin
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Animals
• Aorta (drug effects, enzymology, pathology)
• Arteriosclerosis (enzymology, pathology, physiopathology)
• Cell Division (drug effects)
• Cells, Cultured
• Humans
• Male
• Muscle, Smooth, Vascular (drug effects, enzymology, pathology)
• Natriuretic Peptide, Brain (pharmacology)
• Neprilysin (metabolism)
• Phenylephrine (pharmacology)
• Rabbits
• Vasoconstrictor Agents (pharmacology)
• Vasodilation (drug effects)
• Vasodilator Agents (pharmacology)