Inhibitory effects of angiotensin-(1-7) on the nerve stimulation-induced release of norepinephrine and neuropeptide Y from the mesenteric arterial bed.
Neuropeptide Y (NPY) is a cotransmitter with norepinephrine (NE) and ATP in sympathetic nerves. There is evidence for increased activity of the sympathetic nervous system and the renin-angiotensin system (RAS), as well as a role for NPY in the development of hypertension in experimental animal models and in humans. Angiotensin II (ANG II) is known to facilitate sympathetic neurotransmission, an effect greater in spontaneously hypertensive rats (SHR) than normotensive Wistar-Kyoto (WKY) rats. A newly discovered product of the RAS is angiotensin-(1-7) [ANG-(1-7)]. There is evidence suggesting that ANG-(1-7) opposes the actions of ANG II, resulting in hypotensive effects. The objective of this study was to investigate the role of ANG-(1-7) on the nerve-stimulated overflow of NE and NPY from the mesenteric arterial bed of SHR and the mechanisms involved in mediating any effects produced. ANG-(1-7) (0.001, 0.01, 0.1 microM) decreased nerve-stimulated NE and NPY overflow, as well as perfusion pressure in preparations obtained from SHR. This effect was greater in preparations of SHR than WKY controls. In addition, ANG-(1-7) decreased NE overflow to a greater extent than NPY overflow. Administration of the Mas receptor antagonist, D-Ala(7) ANG-(1-7), attenuated the decrease in both NE and NPY overflow due to ANG-(1-7) administration. However, the angiotensin type 2 receptor antagonist, PD-123391, attenuated the effect of ANG-(1-7) on NE overflow without affecting the decrease in NPY overflow. Moreover, in the presence of N(G)-nitro-L-arginine methyl ester, ANG-(1-7) decreased NPY overflow, but not NE overflow. ANG-(1-7) decreases the nerve-stimulated overflow of NE and NPY in preparations of SHR, whereas ANG II enhances it. Therefore, ANG-(1-7) may counteract the effects of ANG II by acting on ANG type 2 and Mas receptors.
Byku
Mirnela
M
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, St. Louis, Missouri, USA.
Macarthur
Heather
H
Westfall
Thomas C
TC
D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009478:Neuropeptide Y / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D000959:Antihypertensive Agents; D007093:Imidazoles; D009478:Neuropeptide Y; D010446:Peptide Fragments; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; C073402:PD 123319; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine