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

OBJECTIVES We sought to define the vascular actions of the cardiac hormone brain natriuretic peptide (BNP) on cellular proliferation and cyclic guanos ine monophosphate (cGMP) in human aortic vascular smooth muscle cells (HAVS MCs). Secondly, we investigated BNP and acetylcholine (ACh) vasorelaxations in aortic rings from normal and atherosclerotic rabbits in the presence an d absence of long-term oral inhibition of neutral endopeptidase (NEP). BACKGROUND The vascular actions of BNP are not well defined, despite the pr esence of its receptor in vascular smooth muscle and the upregulation of NE P, the ectoenzyme that degrades BNP, in the vascular wall in atherosclerosi s. METHODS HAVSMCs stimulated with fetal calf serum (FCS) were pulsed with bro modeoxyuridine (BrdU) with and without BNP. The HAVSMCs were incubated in t he presence and absence of BNP to assess cGMP. Vasorelaxations to BNP and A Ch were assessed in rings in normal and atherosclerotic rabbits in the pres ence and absence of long-term oral inhibition of NEP, together with assessm ent 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 norma l isolated aortic rings, which were impaired in atherosclerotic versus norm al 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 c ell proliferation and potentiates the generation of cGMP. BNP potently rela xes the normal rabbit aorta, and this response is impaired in atheroscleros is but preserved with inhibition of NEP, together with a reduction in ather oma formation and preservation of relaxations to ACh. (C) 2000 by the Ameri can College of Cardiology.