Addition of highly purified rat angiotensinogen to isolated rat hind limb perfusate increased angiotensin II release 14-fold compared with saline infusion.
The study demonstrates that active renin is present in the vessel wall and can cleave natural angiotensinogen to form angiotensin peptides, supporting the concept that vascular renin is primarily taken up from the circulation.
Effect estimate: 14-fold increase
The cleavage of synthetic tetradecapeptide renin substrate has been used to infer the presence of renin in the walls of isolated blood vessels; however, the conversion of natural angiotensinogen to angiotensin in isolated blood vessels has not been reported. We studied the release 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 radioimmunoassay. Western blot further identified the released material as angiotensinogen. Spontaneous release of angiotensins I and II was demonstrated by high performance liquid chromatography and radioimmunoassay. When highly purified rat angiotensinogen was added to the perfusate, release of angiotensin II was increased 14-fold compared with saline infusion. Captopril (10 mumol/L) inhibited angiotensinogen-induced angiotensin II release by 67% and led to an increase in angiotensin I release by 301%. Bilateral nephrectomy 24 hours before the experiments reduced basal angiotensin release below the detection limit and blunted angiotensinogen-induced angiotensin II formation by 95%. We conclude that active renin is present in the vessel wall and interacts with its natural substrate to form angiotensin peptides. Our data support the notion that the bulk of vascular renin is taken up from the circulation.
Hilgers et al. (Tue,) reported a other. Highly purified rat angiotensinogen vs. Saline infusion was evaluated on Release of angiotensin II (14-fold increase). Addition of highly purified rat angiotensinogen to isolated rat hind limb perfusate increased angiotensin II release 14-fold compared with saline infusion.