Functional evidence for an angiotensin IV receptor in rat resistance arteries

To distinguish between the different effects of angiotensin IV (Ang IV) on resistance artery vasoreactivity, freshly isolated rat mesenteric arteries were perfused and the changes in their diameter were recorded under various conditions. Ang IV exerted vasoconstrictor effects on both normal vessels and vessels that had been precontracted with phenylephrine or serotonin. Th is effect was abolished by losartan or candesartan cilexetil, two type 1 an giotensin receptor antagonists, but not by PD 123319, a type 2 angiotensin receptor antagonist. No tachyphylaxis was observed for the vasoconstrictor effect of Ang IV. N-G-nitro-L-arginine methyl ester, a nitric oxide synthas e inhibitor, had no effect on Ang IV-induced vasoconstriction, whereas indo methacin, a cyclooxygenase inhibitor that was inactive by itself, influence d Ang IV-induced vasoconstriction, suggesting that Ang IV could stimulate t he release of prostaglandins. Treatment of preconstricted vessels by candes artan cilexetil unraveled a vasodilator effect of Ang IV that was abolished by PD 123319, a type 2 angiotensin receptor antagonist. Unexpectedly, Ang IV still produced a vasoconstrictor effect on normal or preconstricted vess els after blockade of both type 1 and type 2 angiotensin receptors. Taken t ogether, these results show that Ang IV influences resistance artery vasore activity via different mechanisms, one of which implicates a functionally a ctive type 4 angiotensin receptor.