Interactions of neuropeptide y, catecholamines, and angiotensin at the vascular neuroeffector junction.

Work from our laboratory has established that angiotensin II (Ang II) produces a greater enhancement of the nerve stimulation (NS)-induced release (overflow) of both norepinephrine (NE) and neuropeptide Y (NPY) and a greater increase in perfusion pressure of the mesenteric arterial bed obtained from the spontaneously hypertensive rat (SHR) compared to age-matched Wistar-Kyoto (WKY) or Sprague-Dawley rats. The enhancement of NS-induced NPY release was blocked by the AT1 receptor antagonist EMD 66684 and the AT2 receptor antagonist PD 123319. Both captopril and EMD 66684 decreased NPY and NE overflow from SHR mesenteric beds, suggesting an endogenous renin-angiotensin system (RAS) is active in the mesenteric artery. We also observed that the recently discovered new arm of the RAS, namely, angiotensin (1-7) (Ang-(1-7)), attenuated the NS-induced increase in NE and NPY release and the accompanied increased perfusion pressure. These inhibitory effects were greater in blood vessels obtained from SHR compared to WKY. We suggest that inhibition of sympathetic neurotransmission contributes to the mechanism(s) by which Ang-(1-7) acts to inhibit the vasoconstrictor effect of Ang II. Administration of the MAS receptor antagonist D-Ala(7)Ang-(1-7) attenuated the decrease in both NE and NPY release due to Ang-(1-7) administration. The AT2 receptor antagonist PD 123391 attenuated the effect of Ang-(1-7) on NE release without affecting the decrease in NPY release. We observed a shift in the balance between Ang II and Ang-(1-7) levels in the SHR with an increase in Ang II and a decrease in Ang-(1-7) in the blood and mesenteric artery. This appears to be due to an increase in angiotensin-converting enzyme (ACE) in the mesenteric artery of the SHR.