Effect of SQ20881 and captopril on pulmonary angiotensin II formation and blood pressure.
The lung is thought to be the major site for conversion of angiotensin I (AI) to angiotensin II (AII), although a significant amount of AI conversion is also known to occur in the peripheral circulation. Reports suggest that pulmonary conversion of AI to AII is more sensitive to inhibition by specific kininase II inhibitors than extrapulmonary conversion. This latter observation prompted us to seek for a dose of SQ20881 and/or captopril that would suppress the conversion of AI to AII in the lung without affecting extrapulmonary conversion of AI and thereby peripheral pressor responses to intravenously administered AI. Experiments were performed on 15 pentobarbital anaesthetized dogs. The AII arterial-venous difference across the lung was measured during an intravenous (i.v.) infusion of AI which produced a steady-state rise in blood pressure of 20 mmHg. This protocol was repeated with the same dose of AI following three graded doses of either SQ20881, captopril or vehicle. Results showed that the systemic pressor response to AI cannot be dissociated from pulmonary AI conversion.
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000096:biosynthesis*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D008168:Lung / Q000378:metabolism*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives*; D013722:Teprotide / Q000494:pharmacology*
D009842:Oligopeptides; D000804:Angiotensin II; D000803:Angiotensin I; D011392:Proline; D002216:Captopril; D013722:Teprotide