Angiotensin II enhances hyperpolarization-activated currents in rat aortic baroreceptor neurons: involvement of superoxide.
As an endogenous physiologically active peptide, angiotensin (ANG) II plays an important role in the maintenance of blood pressure. In the arterial baroreceptor reflex (a pivotal regulator of blood pressure), aortic baroreceptor (AB) neurons located in the nodose ganglia (NG) are a primary afferent limb of the baroreflex. Hyperpolarization-activated currents (I(h)) in the AB neurons contribute to the excitability of the AB neurons. Therefore, the present study was to measure the modulating effect of ANG II on the I(h) in the primary AB neurons isolated from rats. Data from immunofluorescent and Western blot analyses showed that protein of AT(1) and AT(2) receptors was expressed in the nodose neurons. In the whole cell patch-clamp recording, ANG II concentration dependently enhanced the I(h) density in the AB neurons (100 nM ANG II-induced 53.8 +/- 3.8% increase for A-type AB neurons and 30.4 +/- 7.7% increase for C-type AB neurons at test pulse -140 mV, P < 0.05). ANG II also decreased membrane excitability in the AB neurons. AT(1) receptor antagonist (1 muM losartan) but not AT(2) receptor antagonist (1 muM PD-123,319) totally abolished the effect of ANG II on the I(h) and neuronal excitability. In addition, NADPH oxidase inhibitor (100 muM apocynin) and superoxide scavenger (1 mM tempol) also significantly blunted the ANG II-induced increase of the I(h) and decrease of the membrane excitability in the AB neurons. Furthermore, losartan, apocynin, or tempol significantly attenuated the superoxide overproduction in the NG tissues induced by ANG II. These results suggest that ANG II-NADPH oxidase-superoxide signaling can activate the I(h) and subsequently decrease the membrane excitability of rat AB neurons.
Department of Emergency Medicine, Univ. of Nebraska Medical Center, Omaha, NE 68198-1150, USA.
Libin
L
Zhang
Huiyin
H
Tu
Yu-Long
YL
Li
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000294:innervation*; D001794:Blood Pressure / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009620:Nodose Ganglion / Q000187:drug effects / Q000502:physiology*; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000502:physiology; D013481:Superoxides / Q000494:pharmacology
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013481:Superoxides; D000804:Angiotensin II