Angiotensin II-mediated facilitation of sympathetic neurotransmission in the spontaneously hypertensive rat is not associated with neuronal uptake 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 AII in facilitating release of neurotransmitter from sympathetic nerves by a mechanism involving prejunctional angiotensin receptors. In addition, AII may be a substrate for the carrier processes that operate within sympathetic nerves. Therefore, we examined the influence of AII on the responses to sympathetic nerve stimulation in the isolated perfused mesenteric vascular bed preparation and determined whether AII was incorporated into neuronal tissue in blood vessels. AII (10(-8) M) shifted the frequency-response curves to the left, and this shift was reversed with addition of the AII receptor type 1 (AT1) antagonist losartan (10(-6) M). AII uptake into mesenteric artery, thoracic aorta, kidney, and skeletal muscle was determined in tissues taken from SHR and normotensive Wistar-Kyoto rats (WKY). Additional tissues were taken from animals that had been 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 AII accumulation was temperature sensitive and was also sensitive to the metabolic inhibitor 2-4-dinitrophenol (DNP 10(-3) M). The results confirm the role of AII in potentiating the responses to sympathetic nerve stimulation through a process involving AT1 receptors, but this process is not associated with neuronal accumulation of the peptide.
Jonsson
J R
JR
Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia.
Smid
S D
SD
Frewin
D B
DB
Head
R J
RJ
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004558:Electric Stimulation; D007093:Imidazoles / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D019808:Losartan; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D016627:Oxidopamine; D019808:Losartan