Renin uptake by the endothelium mediates vascular angiotensin formation

We investigated the role of the vascular endothelium in the local productio n of angiotensin. Angiotensin release from isolated rat hindquarters perfus ed with an artificial medium was measured by high-performance liquid chroma tography and radioimmunoassay. Perfused hindquarters with endothelium relea sed angiotensin I spontaneously, indicating ongoing renin-angiotensinogen r eaction. Endothelium denudation (by a detergent, validated by electron micr oscopy and by the absence of a vasodilator response to acetylcholine) reduc ed angiotensin I release by >90%, whereas bilateral nephrectomy 24 hours be fore perfusion abolished the release completely. Infusion of renin into per fused hindquarters induced sustained local angiotensin I release in the pre sence of an intact endothelium but not after endothelium denudation. The co nversion of angiotensin I to angiotensin II was abrogated by endothelium de nudation, whereas the disappearance of angiotensin II was unchanged. Endoth elium denudation diminished the pressor response to angiotensin II but abol ished the response to renin and angiotensin I. Expression of renin messenge r RNA, investigated by reverse-transcription polymerase chain reaction usin g 4 different primer combinations, was not detected in up to 5 mug vascular RNA, whereas a renin signal was readily detected with 5 ng kidney RNA. The effects of endothelium destruction on Ang I formation support the notion t hat the endothelium mediates vascular angiotensin formation by taking up re nin.