ANGIOTENSINOGEN IS CLEAVED TO ANGIOTENSIN IN ISOLATED RAT-BLOOD VESSELS

The cleavage of synthetic tetradecapeptide renin substrate has been us ed to infer the presence of renin in the walls of isolated blood vesse ls; however, the conversion of natural angiotensinogen to angiotensin in isolated blood vessels has not been reported. We studied the releas e of angiotensinogen and the formation of angiotensins in a bloodless, perfused, isolated hind limb preparation of the rat. Perfusion with a modified Tyrode's solution resulted in spontaneous release of 4.7+/-1 .5 pmol per 30 minutes of angiotensinogen as measured directly by radi oimmunoassay. Western blot further identified the released material as angiotensinogen. Spontaneous release of angiotensins I and II was dem onstrated by high performance liquid chromatography and radioimmunoass ay. When highly purified rat angiotensinogen was added to the perfusat e, release of angiotensin II was increased 14-fold compared with salin e infusion. Captopril (10 mumol/L) inhibited angiotensinogen-induced a ngiotensin II release by 67% and led to an increase in angiotensin I r elease by 301%. Bilateral nephrectomy 24 hours before the experiments reduced basal angiotensin release below the detection limit and blunte d angiotensinogen-induced angiotensin II formation by 95%. We conclude that active renin is present in the vessel wall and interacts with it s natural substrate to form angiotensin peptides. Our data support the notion that the bulk of vascular renin is taken up from the circulati on.