Significance of vascular renin for local generation of angiotensins.
The effects of specific renin inhibitors, angiotensin converting enzyme inhibitors, indomethacin, and prostaglandin I2 analogue on the release of angiotensins from isolated and Krebs-Ringer-perfused rabbit mesenteric arteries were examined. Three different renin inhibitors suppressed release of angiotensins in dose-dependent manners. At the highest concentration (10(-7) M), the inhibitors EMD 52,620, EMD 54,388, and EMD 52,742 induced 46%, 52%, and 48% decreases, respectively, in the basal rate of immunoreactive angiotensin II release. These results provide clear evidence that released angiotensins are produced by the specific action of vascular renin and that the renin inhibitors suppress the vascular renin-angiotensin system as well as the circulating renin-angiotensin system and appear to provide a useful mode for the treatment of hypertension. Nonsulfhydryl angiotensin converting enzyme inhibitors cilazapril and delapril were more effective than captopril, and ramipril was equipotent to captopril, suggesting that the effectiveness of angiotensin converting enzyme inhibitors on the vascular renin-angiotensin system cannot be explained only by its inhibitory effect on angiotensin converting enzyme. Indomethacin, which was reported to suppress angiotensin II release from rat hind limbs, elicited a dose-dependent increase of angiotensin release from rabbit mesenteric arteries. These results suggest that a difference exists in the regulatory mechanisms in the release of angiotensins from diverse vascular beds.
Higashimori
K
K
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tenn 37232.
Gante
J
J
Holzemann
G
G
Inagami
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000809:Angiotensins / Q000096:biosynthesis*; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D012083:Renin / Q000502:physiology*; D000092502:Renin Inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D011464:Epoprostenol; D007213:Indomethacin; D012083:Renin; D000092502:Renin Inhibitors; C035847:ataprost