Cardiac sympathetic afferent stimulation by bradykinin in heart failure: role of NO and prostaglandins.
I have shown that cardiac sympathetic afferent stimulation by epicardial application of bradykinin (BK) was significantly enhanced in pacing-induced heart failure (HF) dogs. This enhancement appeared to be mediated by prostaglandins. The present study was to determine whether nitric oxide is involved in this enhancement. Under alpha-chloralose (100 mg/kg iv) anesthesia, the renal sympathetic nerve activity (RSNA) response to BK was determined in 15 HF and 15 sham dogs in the sinoaortic-denervated and vagotomized state. The RSNA response to BK was significantly enhanced in HF. This enhanced RSNA response to BK was significantly reduced in the HF dogs after administration of the cycloxygenase inhibitor indomethacin (5 mg/kg iv), but no significant change was found in the sham group. In contrast, RSNA responses to BK were significantly reduced in the sham dogs after administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg iv), but no significant change was found in the HF group. These data suggest that the RSNA response to BK is mediated by nitric oxide to a large degree in the normal state but is primarily mediated by prostaglandins in the HF state.
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha, Nebraska 68198-4575, USA.
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D000344:Afferent Pathways / Q000187:drug effects*; D000818:Animals; D002303:Cardiac Output, Low / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000294:innervation*; D006439:Hemodynamics; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000294:innervation; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin