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 AT(4) 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 hemo dynamic responses to activation of the putative AT(4) receptor were studied in anesthetized rats by left renal arterial infusion of two endogenous lig ands, angiotensin IV and LW-hemorphin-7. Angiotensin IV (10, 100, and 1,000 pmol/min) infusion caused dose-dependent reductions in blood flow to the i nfused kidney, which were abolished by pretreatment with losartan. In respe ct to this effect, angiotensin IV was similar to 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. Int rarenal infusion of LVV-hemorphin-7 (10, 100, and 1,000 pmol/min) had no si gnificant effect on renal blood flow in the infused and noninfused kidneys, or on mean arterial pressure or heart rate. These results provide no evide nce for a renal vasodilatory action of angiotensin IV or LVV-hemorphin-7. O n the contrary, intrarenal angiotensin TV infusion produced vasoconstrictio n of the renal vasculature, mediated by activation of AT(1) receptors. Thes e observations provide evidence against a vasodilatory role of putative AT( 4) receptors in the rat kidney.