title: Persistent inhibition of the pressor and aldosterone responses to angiotensin-II by TCV-116 in normotensive subjects.
abstract: TCV-116 is an orally active, nonpeptide antagonist of angiotensin-II type-1 receptor. The angiotensin-II antagonistic potency of TCV-116 was evaluated in normal volunteers. TCV-116 was administered at single doses of 1, 2.5, and 5 mg orally on separated days. Before, and 4, 8, and 24 h after the drug administration, angiotensin-II was infused intravenously at the rate of 2.5 to 40 ng/kg/min for 5 min each. At 2.5 mg of TCV-116, the pressor response to angiotensin-II was significantly suppressed at 4 and 8 hours after drug administration. TCV-116 at 5 mg produced a reduction of basal blood pressure and a suppression of pressor response to angiotensin-II, which persisted for 24 h. Aldosterone response to exogenous angiotensin-II was suppressed to 10% at 8 h after 5 mg of TCV-116 administration and remained suppressed to 48% until 24 h. These results suggest that TCV-116 is a highly potent and long-lasting antagonist of angiotensin-II receptor in man. The renin-angiotensin system may play a role in the regulation of blood pressure even in normotensive subjects.
authors.affiliation: Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ogihara
authors.forename: M
authors.initials: M
authors.lastname: Nagano
authors.forename: J
authors.initials: J
authors.lastname: Higaki
authors.forename: K
authors.initials: K
authors.lastname: Kohara
authors.forename: H
authors.initials: H
authors.lastname: Mikami
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000450:Aldosterone / Q000097:blood*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000502:physiology*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D006801:Humans; D008297:Male; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; C077793:candesartan cilexetil