Alternative Angiotensin II Formation in Rat Arteries Occurs Only at Very High Concentrations of Angiotensin I

Abstract

Abstract —Contrary to previous reports, recent enzymatic assays showed the predominance of chymase-like activity in rat arteries. We determined the existence and significance of such alternative pathways in rat carotid arteries by measuring contraction of arterial rings in organ baths and blood pressure in conscious rats. Hamster aorta served as a positive control for chymase. Temocapril (30 μmol/L) inhibited the contractions to angiotensin (Ang) I (10 ⁻⁹ to 10 ⁻⁵ mol/L) except at high concentrations of Ang I (>10 ⁻⁷ mol/L). Addition of chymostatin (100 μmol/L) to temocapril exerted a synergistic inhibitory effect. Hamster aorta gave similar results, except that temocapril was 30-fold less effective than in rat arteries. [Pro ¹¹ , d -Ala ¹² ]Ang I (10 ⁻⁸ to 10 ⁻⁵ mol/L), a chymase-specific substrate, provoked similar responses in rat and hamster arteries; chymostatin, but not temocapril, attenuated the responses. CV 11974 (30 μmol/L), an Ang II type 1 receptor antagonist, abolished the responses to both peptides. In conscious rats, Ang I (0.03 to 30 μg/kg) and [Pro ¹¹ , d -Ala ¹² ]Ang I (7 to 700 μg/kg) produced similar pressor responses. Not only CV 11974 (1 mg/kg) but also temocapril (2 mg/kg) abolished Ang I–induced responses in vivo. CV 11974, but not temocapril, inhibited responses to [Pro ¹¹ , d -Ala ¹² ]Ang I. Our results showed the presence of the alternative pathway in rat arteries, but it did not play a major role. Arteries with the opposing characteristics of chymase responded equally to [Pro ¹¹ , d -Ala ¹² ]Ang I. These findings suggest that biochemical and [Pro ¹¹ , d -Ala ¹² ]Ang I–derived results may not reflect the functional significance of chymase.