TY - JOUR
T1 - Interaction of central Ang II and NO on the cardiac sympathetic afferent reflex in dogs
AU - Ma, Rong
AU - Zhu, Guo Qing
AU - Wang, Wei
N1 - Funding Information:
This study was supported by NINgrants #PO-1 HL62222, RO-1 HL077691 and a Grant-on-Aid from the American Heart Association. The author wishes to thank Dr. Irving N. Zucker for his critical. Losartan was kindly provided by the DuPont-Merck, California.
PY - 2005/3/31
Y1 - 2005/3/31
N2 - The aim of this study was to test the hypothesis that the central angiotensin II (Ang II) and nitric oxide (NO) systems interact to modulate the cardiac sympathetic afferent reflex (CSAR). All dogs were anesthetized with α-chloralose (100 mg/kg, iv). They were sino-aortic baroreceptor denervated and vagotomized throughout the experiment renal sympathetic nerve activity responses to cardiac sympathetic afferent stimulation and the central gain of the CSAR were measured. Three protocols were performed: (1) intracerebroventricular injection (icv, 3 μg/h or 6 μg/h) of Ang II with and without Nω-nitro-L-arginine methyl ester (L-NAME) (icv, 1 mg/kg), (2) L-NAME (icv) with and without Ang II (icv, 6 μg/h), and (3) administration of the specific neural NO synthase (nNOS) inhibitor, S-Methyl-L-thiocitrulline (MeTC) (icv, 0.1 or 1 mM, 0.5 ml in 5 min) with and without pretreatment with the angiotensin type 1 receptor antagonist, losartan (icv, 0.125 mg/kg). The primary findings were (1) Ang II alone did not significantly affect the central sensitivity of the CSAR. However, Ang II with L-NAME enhanced this reflex, (2) even though L-NAME alone augmented the CSAR, this excitatory effect was further potentiated in the presence of Ang II and (3) MeTC significantly enhanced the central sensitivity of the CSAR. However, this enhancement did not occur after pretreatment with losartan. These data suggest that Ang II interacts with NO in the brain to modulate the CSAR and that inhibition of NO is required for facilitation of the CSAR by Ang II.
AB - The aim of this study was to test the hypothesis that the central angiotensin II (Ang II) and nitric oxide (NO) systems interact to modulate the cardiac sympathetic afferent reflex (CSAR). All dogs were anesthetized with α-chloralose (100 mg/kg, iv). They were sino-aortic baroreceptor denervated and vagotomized throughout the experiment renal sympathetic nerve activity responses to cardiac sympathetic afferent stimulation and the central gain of the CSAR were measured. Three protocols were performed: (1) intracerebroventricular injection (icv, 3 μg/h or 6 μg/h) of Ang II with and without Nω-nitro-L-arginine methyl ester (L-NAME) (icv, 1 mg/kg), (2) L-NAME (icv) with and without Ang II (icv, 6 μg/h), and (3) administration of the specific neural NO synthase (nNOS) inhibitor, S-Methyl-L-thiocitrulline (MeTC) (icv, 0.1 or 1 mM, 0.5 ml in 5 min) with and without pretreatment with the angiotensin type 1 receptor antagonist, losartan (icv, 0.125 mg/kg). The primary findings were (1) Ang II alone did not significantly affect the central sensitivity of the CSAR. However, Ang II with L-NAME enhanced this reflex, (2) even though L-NAME alone augmented the CSAR, this excitatory effect was further potentiated in the presence of Ang II and (3) MeTC significantly enhanced the central sensitivity of the CSAR. However, this enhancement did not occur after pretreatment with losartan. These data suggest that Ang II interacts with NO in the brain to modulate the CSAR and that inhibition of NO is required for facilitation of the CSAR by Ang II.
KW - Angiotensin II
KW - Cerebroventricle
KW - L-NAME
KW - Losartan
KW - Nitric oxide synthase
KW - Renal sympathetic nerve activity
KW - S-Metyl-L-thiocitrulline
UR - http://www.scopus.com/inward/record.url?scp=15944378478&partnerID=8YFLogxK
U2 - 10.1016/j.autneu.2004.12.007
DO - 10.1016/j.autneu.2004.12.007
M3 - Article
C2 - 15795177
AN - SCOPUS:15944378478
SN - 1566-0702
VL - 118
SP - 51
EP - 60
JO - Autonomic Neuroscience: Basic and Clinical
JF - Autonomic Neuroscience: Basic and Clinical
IS - 1-2
ER -