Renal hemodynamic responses to intrarenal infusion of ligands for the putative angiotensin IV receptor in anesthetized rats.
Angiotensin IV, a hexapeptide fragment (3-8) of angiotensin II metabolism, has been reported to produce vasodilatation within the renal vasculature by activation of the putative AT4 receptor. However, there are conflicting findings, with previous in vivo studies providing evidence for and against a renal vasodilator action of angiotensin IV. In this study, the renal hemodynamic responses to activation of the putative AT4 receptor were studied in anesthetized rats by left renal arterial infusion of two endogenous ligands, angiotensin IV and LVV-hemorphin-7. Angiotensin IV (10, 100, and 1,000 pmol/min) infusion caused dose-dependent reductions in blood flow to the infused kidney, which were abolished by pretreatment with losartan. In respect to this effect, angiotensin IV was approximately 300-fold less potent than angiotensin II. There were no significant effects of angiotensin IV on mean arterial pressure, heart rate, or blood flow to the noninfused kidney. Intrarenal infusion of LVV-hemorphin-7 (10, 100, and 1,000 pmol/min) had no significant effect on renal blood flow in the infused and noninfused kidneys, or on mean arterial pressure or heart rate. These results provide no evidence for a renal vasodilatory action of angiotensin IV or LVV-hemorphin-7. On the contrary, intrarenal angiotensin IV infusion produced vasoconstriction of the renal vasculature, mediated by activation of AT1 receptors. These observations provide evidence against a vasodilatory role of putative AT4 receptors in the rat kidney.
Fitzgerald
S M
SM
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, USA.
Evans
R G
RG
Bergström
G
G
Anderson
W P
WP
D000758:Anesthesia; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects*
C090830:AT4 receptor; D006454:Hemoglobins; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; C074309:LVV-hemorphin-7; D019808:Losartan