Suppression of angiotensin II release by prostaglandin synthesis inhibitors in hind legs.
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.
Mizuno
K
K
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
Higashimori
K
K
Inagami
T
T
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*
D011453:Prostaglandins; D011943:Receptors, Adrenergic, beta; D062367:ortho-Aminobenzoates; D000804:Angiotensin II; D008469:Meclofenamic Acid; D000803:Angiotensin I; D011433:Propranolol; D007545:Isoproterenol; D007213:Indomethacin