title: Effects of proangiotensin-12 infused continuously over 14 days in conscious rats.
abstract: 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.
authors.affiliation: Department of Nutrition Science, Minami Kyusyu University, Miyazaki 880-0032, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Kida
authors.forename: Naomi
authors.initials: N
authors.lastname: Nozaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuwasako
authors.forename: Sayaka
authors.initials: S
authors.lastname: Nagata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitamura
authors.forename: Johji
authors.initials: J
authors.lastname: Kato
mesh_terms: D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000808:Angiotensinogen / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D006332:Cardiomegaly / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D055104:Infusions, Subcutaneous; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D015430:Weight Gain / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; C515557:proangiotensin-12, rat; D000808:Angiotensinogen; D000804:Angiotensin II; D000450:Aldosterone