Effects of proangiotensin-12 infused continuously over 14Â days in conscious rats

The carboxyl terminal-extended form of angiotensin I, proangotensin-12, was recently identified in rat tissues including the small intestine, cardiac ventricles, and kidneys. Single administration of proangiotensin-12 exerts vasoconstrictor and pressor effects, probably by conversion to angiotensin II; however, there are currently no data available about the subacute effects of proangiotensin-12. In the present study, we examined the effects of prolonged infusion of proangiotensin-12 in conscious rats. Continuous, subcutaneous infusion of 240 pmol/kg/min of proangiotensin-12 gradually elevated blood pressure over 14 days, as did the same dose of angiotensin II. The pressor effects of proangiotensin-12 were abolished by oral administration of losartan, an angiotensin II type 1 receptor blocker, or perindopril, an angiotensin converting enzyme (ACE) inhibitor. Meanwhile, angiotensin II-induced elevation of blood pressure was inhibited by losartan but not by perindopril. Both the plasma aldosterone level and heart weight/body weight ratio were increased by the prolonged infusion of proangiotensin-12, but these increases were attenuated by losartan and perindopril. The present results suggest that proangiotensin-12 infused continuously over 14 days exerts pressor effects accompanied with the elevation of plasma aldosterone and cardiac hypertrophy in an ACE- and angiotensin II type 1 receptor-dependent manner.