Ferro C, Haynes W, Webb D
Neutral endopeptidase inhibitors cause vasoconstriction in man
16th Scientific Meeting of the International Society of Hypertension
ISH Abstract Book (Jun) 16: 1996

Thiorphan, a neutral endopeptidase (NEP) inhibitor, caused vasoconstriction in the forearm as assesed by plethysmography in normal subjects. This action was not attenuated by enalapril. Another NEP inhibitor had a simlar vasoconstrictive effect.

Comment: NEP degrades ANP and NEP inhibitors raise ANP and were briefly seen as potential antihypertensive agents. This study demonstrates that they can have the opposite effect, probably by inhibiting degradation of endothelin but not Ang II which are also degraded by NEP. The effects of these agents probably depends on prevailing levels of Ang II, endothelin and other regulatory influences eg sodium and volume status. If the patient is salt and volume loaded to suppress the renin-angiotensin system, and ET, these agents may increase ANP they reduce BP; otherwise they may paradoxically increase the blood pressure. (Alan Jardine, M.D., Glasgow University, Scotland).

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16th Scientific Meeting of the International Society of Hypertension
H: Drug therapy : ACE inhibitors