title: Role of blood flow in carotid body chemoreflex function in heart failure.
abstract: Peripheral chemoreflex sensitivity is potentiated in clinical and experimental chronic heart failure (CHF). Blood supply to tissues is inevitably reduced in CHF. However, it remains poorly understood whether the reduced blood flow is the cause of increased peripheral chemoreflex sensitivity in CHF. This work highlights the effect of chronically reduced blood flow to the carotid body (CB) on peripheral chemoreflex function in rabbits. In pacing-induced CHF rabbits, blood flow in the carotid artery was reduced by 36.4 ± 5.2% after 3 weeks of pacing. For comparison, a similar level of blood flow reduction was induced by carotid artery occlusion (CAO) over a similar 3 week time course without pacing. CB blood supply was reduced by similar levels in both CHF and CAO rabbits as measured with fluorescent microspheres. Compared with sham rabbits, CAO enhanced peripheral chemoreflex sensitivity in vivo, increased CB chemoreceptor activity in an isolated CB preparation and decreased outward potassium current (Ik) in CB glomus cells to levels similar to those that were observed in CHF rabbits. In CAO CB compared to sham, neural nitric oxide (NO) synthase (nNOS) expression and NO levels were suppressed, and angiotensin II (Ang II) type 1 receptor (AT1-R) protein expression and Ang II concentration were elevated; these changes were similar to those seen in the CB from CHF rabbits. A NO donor and AT1-R antagonist reversed CAO-enhanced chemoreflex sensitivity. These results suggest that a reduction of blood flow to the CB is involved in the augmentation of peripheral chemoreflex sensitivity in CHF.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Ding
authors.forename: Yu-Long
authors.initials: YL
authors.lastname: Li
authors.forename: Harold D
authors.initials: HD
authors.lastname: Schultz
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity; D002304:Cardiac Pacing, Artificial; D002339:Carotid Arteries / Q000294:innervation* / Q000503:physiopathology* / Q000601:surgery; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D003250:Constriction; D004195:Disease Models, Animal; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D012039:Regional Blood Flow; D013050:Spectrometry, Fluorescence; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D020030:Nitric Oxide Donors; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D011188:Potassium