Interaction of central Ang II and NO on the cardiac sympathetic afferent reflex in dogs.
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 alpha-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 microg/h or 6 microg/h) of Ang II with and without N(omega)-nitro-L-arginine methyl ester (L-NAME) (icv, 1 mg/kg), (2) L-NAME (icv) with and without Ang II (icv, 6 microg/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.
Ma
Rong
R
Department of Cellular and Integrative Physiology, University of Nebraska College of Medicine, 985850 Nebraska Medical Center Omaha, NE 68198-5850, USA.
Zhu
Guo-Qing
GQ
Wang
Wei
W
D000344:Afferent Pathways / Q000187:drug effects* / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002956:Citrulline / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004333:Drug Administration Routes; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013562:Sympathectomy / Q000379:methods; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014628:Vagotomy / Q000379:methods
D047228:Angiotensin II Type 1 Receptor Blockers; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D002956:Citrulline; D009569:Nitric Oxide; D013890:Thiourea; D019808:Losartan; C086717:S-methylthiocitrulline; D019331:NG-Nitroarginine Methyl Ester