Chronic central infusion of ANG II potentiates cardiac sympathetic afferent reflex in dogs.
The aims of this study were to determine whether ANG II is involved in the central integration of the cardiac sympathetic afferent reflex (CSAR), and if this central effect of ANG II is mediated by the AT(1) receptor. Experiments were undertaken in dogs that were anesthetized with alpha-chloralose, sinoaortic denervated, and vagotomized. The renal sympathetic nerve activity (RSNA) responses to varying frequency and voltage stimulation of cardiac sympathetic afferent nerves were used to evaluate the central sensitivity of the CSAR. In two groups of dogs, two doses (50 and 100 ng/min icv) of ANG II were acutely infused. In a third group of dogs, ANG II was chronically infused for 3 days (100 ng/min, 1 microliter/h icv). We found that acute infusion into the cerebroventricle of two doses of ANG II did not affect the central sensitivity of the CSAR or the baseline hemodynamics, but the baseline RSNA increased significantly during the infusion of the higher dose of ANG II. However, chronic intracerebroventricular infusion of ANG II enhanced the central sensitivity of the CSAR significantly. In addition, chronic intracerebrovetricular infusion of ANG II elicited a significant increase in water intake and in arterial pressure from the first and second day of infusion, respectively. In the group that received chronic intracerebroventricular infusion of ANG II, the administration of an AT(1)-receptor antagonist losartan (0.125 mg/kg icv) abolished ANG II-induced augmentation of the CSAR. These results suggest that chronic elevation of central ANG II can sensitize the CSAR via central AT(1) receptors.
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha, Nebraska 68198-4575, USA.
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D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D002552:Cerebral Ventricles; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000294:innervation*; D007263:Infusions, Parenteral; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D019808:Losartan