Modulation Of Norepinephrine And Neuropeptide Y Release By Angiotensin-(1-7) From The Mesenteric Arterial Bed Of The Rat: Role Of Cyclooxygenase

Ang‐(1‐7) produces a significant decreasein the nerve stimulation (NS)‐induced release of the sympathetic nervous system cotransmitters NE and NPY, as well as perfusion pressure of the mesentericarterial bed of the rat. These effects are greater in mesenteric beds obtained from Spontaneously Hypertensive Rats (SHR) compared to its normotensive control, Wistar‐Kyoto rats (WKY). We examined the hypothesis that the Ang‐(1‐7) induced inhibition of sympathetic neurotransmission is mediated at least in part by prostacyclin (PGI 2 ). Experiments were performed using mesenteric beds obtained from 10–12 week old SHR and WKY rats. The effect of Ang‐(1‐7) on the NS‐evokedrelease of NE and NPY was determined before and after the administration of the COX inhibitor Indomethacin (to prevent PGI 2 synthesis) and the IP receptor antagonist CAY 10441. A reversal of the attenuation of NE and NPY release by Ang‐(1‐7) was observed in the presence of Indomethacin in both SHR and WKY. A trend was observed suggesting CAY10441 is partially reversing the attenuation of NE and NPY release from SHR mesenteric beds, but not WKY. The attenuation of perfusion pressure by Ang‐(1‐7) was reversed by both Indomethacin and CAY10441 in SHR, but not in WKY. These data suggest a role of PGI 2 mediating vasodilation and the inhibition of sympathetic neurotransmission by Ang‐(1‐7). (Supported by HL60260 and NIGMS008306)