| Characterization of antihypertensive activity of ABBOTT-81988, a nonpeptide angiotensin II antagonist in the renal hypertensive rat. | |
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MedLine Citation:
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PMID: 8301584 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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2-(N-Propyl-N[(2'-[1H-tetrazol-5-yl]biphenyl-4yl)methyl]amin o) pyridine-3-carboxylic acid (ABBOTT-81988), a novel nonpeptide angiotensin II (AII) antagonist, was evaluated to characterize its antihypertensive activity in the conscious renal hypertensive rat. Oral or i.v. administration of ABBOTT-81988 at 0.03 to 0.3 mg/kg produced a dose-dependent, sustained decrease in mean arterial pressure (MAP; control 162-173 mm Hg, n = 27) of approximately 20 to 70 mm Hg. At a dose of 0.3 mg/kg p.o., ABBOTT-81988 lowered MAP to a normotensive level for more than 24 hr and did not change heart rate. During its antihypertensive effect (delta MAP, -28% approximately -35%), ABBOTT-81988 (0.1-03 mg/kg i.v.) decreased total peripheral resistance (delta resistance, -31% approximately -43%), and cardiac output remained either unchanged or slightly elevated. ABBOTT-81988 (0.3 mg/kg i.v.) produced an additional antihypertensive effect (delta MAP, -12 +/- 2%, n = 5) in captopril-pretreated (10 mg/kg i.v.) hypertensive rats, but captopril (10 mg/kg i.v.) had no effect in ABBOTT-81988-pretreated (0.3 mg/kg i.v.) rats. In the normotensive rat, ABBOTT-81988 (0.3 mg/kg p.o.) had no effect on basal MAP, but it inhibited the AII-induced (0.1 microgram/kg i.v.) pressor response by 51% to 91% for 24 hr, whereas the responses to norepinephrine (0.3 microgram/kg i.v.), vasopressin (0.03 IU/kg i.v.) and bradykinin (3 micrograms/kg i.v.) were not affected. It is concluded that ABBOTT-81988 is a safe and efficacious AII antagonist that may have use in the treatment of human hypertension. |
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Authors:
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J Y Lee; S A Buckner; M E Brune; R B Warner; M Winn; B De; T M Zydowsky; T J Opgenorth; D J Kerkman; J F Debernardis |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 268 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1994 Jan |
Date Detail:
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Created Date: 1994-03-10 Completed Date: 1994-03-10 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 427-33 Citation Subset: IM |
Affiliation:
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Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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antagonists & inhibitors* Animals Antihypertensive Agents / pharmacology*, therapeutic use Bradykinin / pharmacology Electrocardiography / drug effects Hemodynamics / drug effects Hypertension, Renal / drug therapy* Male Nicotinic Acids / pharmacology* Norepinephrine / pharmacology Rats Rats, Sprague-Dawley Tetrazoles / pharmacology* Vasopressins / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Nicotinic Acids; 0/Tetrazoles; 11000-17-2/Vasopressins; 11128-99-7/Angiotensin II; 141887-34-5/A 81988; 51-41-2/Norepinephrine; 58-82-2/Bradykinin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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