ANGIOTENSIN-II-MEDIATED FACILITATION OF SYMPATHETIC NEUROTRANSMISSIONIN THE SPONTANEOUSLY HYPERTENSIVE RAT IS NOT ASSOCIATED WITH NEURONALUPTAKE OF THE PEPTIDE

Evidence suggests that angiotensin II (AII) can modulate neuroeffector responses in the vasculature of spontaneously hypertensive rats (SHR) . Included in this modulation is an action of All in facilitating rele ase of neurotransmitter from sympathetic nerves by a mechanism involvi ng prejunctional angiotensin receptors. In addition, All may be a subs trate for the carrier processes that operate within sympathetic nerves . Therefore, we examined the influence of All on the responses to symp athetic nerve stimulation in the isolated perfused mesenteric vascular bed preparation and determined whether All was incorporated into neur onal tissue in blood vessels. AII (10(-8) M) shifted the frequency-res ponse curves to the left, and this shift was reversed with addition of the All receptor type 1 (AT1) antagonist losartan (10(-6) M). All upt ake into mesenteric artery, thoracic aorta, kidney, and skeletal muscl e was determined in tissues taken from SHR and normotensive Wistar-Kyo to rats (WKY). Additional tissues were taken from animals that had bee n subjected to chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Although AII accumulation was evident in all tissues examined, in no case was this accumulation diminished by 6-OHDA treatment. Subsequent studies using segments of kidney and skeletal muscle demonstrated that a large proportion of All accumulation was temperature sensitive and was also sensitive to the metabolic inhibitor 2-4-dinitrophenol (DNP 1 0(-3) M). The results confirm the role of AII in potentiating the resp onses to sympathetic nerve stimulation through a process involving AT1 receptors, but this process is not associated with neuronal accumulat ion of the peptide.