Biphasic actions of angiotensin IV on renal blood flow in the rat.
Our aim was to investigate the changes in renal blood flow during brief exposure of the renal vasculature to angiotensin IV (Ang IV). Total renal blood flow was measured by electromagnetic flowmetry in pentobarbital-anesthetized male Sprague Dawley rats. Intrarenal injection of Ang I, Ang II and Ang III produced a dose-dependent vasoconstriction. In contrast, Ang IV and Ang-(3-10) produced a dose-dependent rapid vasoconstriction (lasting seconds) followed by a transient vasodilatation (lasting minutes). The biphasic response to Ang IV was unchanged in rats pre-treated with captopril, whereas the Ang-(3-10) response was abolished implying that its vasoactive activity was due to the generation of Ang IV. The vasodilatory component of Ang IV was unaffected by indomethacin. The biphasic vasoactive response of Ang IV was unaffected by divalinal-Ang IV (AT(4) receptor antagonist) or PD 123319 (AT(2) receptor antagonist), but greatly reduced by losartan or L-158,809 (AT(1) receptor antagonists). These results suggest that Ang IV is distinct from other angiotensins in that it possesses non-prostaglandin mediated renal vasodilatory activity that is apparently linked to the renal vascular AT(1) receptor.
Handa
Rajash K
RK
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, 46202, USA. rajash_handa@hotmail.com
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D014665:Vasodilator Agents; D000804:Angiotensin II; C073402:PD 123319; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D011451:Prostaglandin-Endoperoxide Synthases; D019808:Losartan; D007213:Indomethacin