title: Suppression of angiotensin II release by prostaglandin synthesis inhibitors in hind legs.
abstract: Previously we reported that immunoreactive angiotensin II (Ang II) release from isolated perfused rat mesenteric arteries was mediated by beta-adrenergic receptor activation. However, the precise mechanism of regulation of vascular renin-angiotensin is not completely understood. In this study, we examined the effect of indomethacin and meclofenamate on immunoreactive angiotensin I (Ang I) and immunoreactive Ang II release from perfused rat hind leg vasculature to delineate the possible relevance of prostaglandins to the vascular renin-angiotensin system in vitro. We also examined the effects of isoproterenol and propranolol on the immunoreactive Ang I and II release. Isolated rat hind legs were perfused with Krebs-Ringer solution, and immunoreactive Ang I and II released into the perfusate were measured directly by using a Sep-Pak C18 cartridge connected to the perfusion system. Indomethacin and meclofenamate (10(-8) to 2 X 10(-6) M) added to the perfusion medium suppressed immunoreactive Ang I and II release to similar extents in a dose-dependent manner (p less than 0.001); the maximal percent inhibition of immunoreactive Ang II release evoked by these inhibitors (2 X 10(-6) M) was 60 +/- 6% (p less than 0.001) for indomethacin and 50 +/- 4% (p less than 0.001) for meclofenamate. Isoproterenol (10(-6) M) failed to cause a change in the release of both peptides, but propranolol (10(-6) M) slightly decreased the release of immunoreactive Ang I and II by 28 +/- 4% (p less than 0.001) and 32 +/- 4% (p less than 0.001), respectively. There was a highly significant positive correlation between the released amount of immunoreactive Ang I and that of immunoreactive Ang II altered by indomethacin (r = 0.91), meclofenamate (r = 0.94), or propranolol administration (r = 0.90). These results suggest that the renin-angiotensin in the hind legs is modulated by prostaglandins and that a difference exists in the beta-adrenergic receptor-mediated release of Ang II among diverse vascular beds.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: K
authors.initials: K
authors.lastname: Mizuno
authors.forename: K
authors.initials: K
authors.lastname: Higashimori
authors.forename: T
authors.initials: T
authors.lastname: Inagami
mesh_terms: D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000098:blood supply*; D007213:Indomethacin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D011453:Prostaglandins; D011943:Receptors, Adrenergic, beta; D062367:ortho-Aminobenzoates; D000804:Angiotensin II; D008469:Meclofenamic Acid; D000803:Angiotensin I; D011433:Propranolol; D007545:Isoproterenol; D007213:Indomethacin