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Enhancement of losartan (DuP 753)-induced angiotensin II receptor antagonism by PD123177 in rats |
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| Authors: | Paneras C. Wong David D. Christ Pieter B. M. W. M. Timmermans |
| Affiliation: | * Cardiovascular Diseases Research, The Du Pont Merck Pharmaceutical Company, Wilmington, DE, USA a Drug Metabolism and Pharmacokinetics Sections, The Du Pont Merck Pharmaceutical Company, Wilmington, DE, USA |
| Abstract: | Losartan (DuP 753) and PD123177 are angiotensin II type 1 (AT1) and type 2 (AT2) receptor selective ligands, respectively. In rats, PD123177 did not exhibit angiotensin II antagonism or hypotensive activity but enhanced these activities of a submaximal dose of losartan. As PD123177 displaced losartan from its rat plasma protein binding sites and thus increased the free concentration of losartan, this may account for its enhancement of the in vivo activities of losartan in rats. |
| Keywords: | Angiotensin II receptor antagonists Antihypcrtcnsivc agents Protein binding Renin-angiotcnsin system |
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