AIMS: Peripheral chemoreflex sensitivity is potentiated in both clinical and experimental chronic heart failure (CHF). NADPH oxidase-derived superoxide mediates angiotensin II (Ang II)-enhanced carotid body (CB) chemoreceptor sensitivity in CHF rabbits, and tempol, the superoxide dismutase (SOD) mimetic, inhibits this Ang II- and CHF-enhanced superoxide anion effect. Here we investigated the role of cytoplasmic SOD [CuZn superoxide dismutase (CuZnSOD)] in the CB on chemoreceptor activity and function in CHF rabbits. METHODS AND RESULTS: CuZnSOD protein expression was decreased in CBs from CHF rabbits vs. sham (P < 0.05). Adenoviral CuZnSOD (Ad CuZnSOD) gene transfer to the CBs increased CuZnSOD protein expression and significantly reduced the baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in the CHF rabbits (P < 0.05). Single-fibre discharge from CB chemoafferents during normoxia (baseline, at approximately 100 mmHg PO2) and in response to hypoxia were enhanced in CHF vs. sham rabbits (P < 0.05). Ad CuZnSOD decreased the baseline discharge (7.6 +/- 1.3 vs. 12.6 +/- 1.7 imp/s at approximately 100 mmHg PO2) and the response to hypoxia (22.4 +/- 1.6 vs. 32.3 +/- 1.2 imp/s at approximately 40 mmHg PO2, P < 0.05) in CHF rabbits. Ad CuZnSOD also normalized the blunted outward K+ current (IK) in CB glomus cells from CHF rabbits (369 +/- 14 vs. 565 +/- 31 pA/pF at +70 mV, P < 0.05). In addition, Ad CuZnSOD reduced the elevation of superoxide level in CBs from CHF rabbits. CONCLUSION: Downregulation of CuZnSOD in the CB contributes to the enhanced activity of CB chemoreceptors and chemoreflex function in CHF rabbits.
AIMS: Peripheral chemoreflex sensitivity is potentiated in both clinical and experimental chronic heart failure (CHF). NADPH oxidase-derived superoxide mediates angiotensin II (Ang II)-enhanced carotid body (CB) chemoreceptor sensitivity in CHF rabbits, and tempol, the superoxide dismutase (SOD) mimetic, inhibits this Ang II- and CHF-enhanced superoxide anion effect. Here we investigated the role of cytoplasmic SOD [CuZn superoxide dismutase (CuZnSOD)] in the CB on chemoreceptor activity and function in CHF rabbits. METHODS AND RESULTS:CuZnSOD protein expression was decreased in CBs from CHF rabbits vs. sham (P < 0.05). Adenoviral CuZnSOD (Ad CuZnSOD) gene transfer to the CBs increased CuZnSOD protein expression and significantly reduced the baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in the CHF rabbits (P < 0.05). Single-fibre discharge from CB chemoafferents during normoxia (baseline, at approximately 100 mmHg PO2) and in response to hypoxia were enhanced in CHF vs. sham rabbits (P < 0.05). Ad CuZnSOD decreased the baseline discharge (7.6 +/- 1.3 vs. 12.6 +/- 1.7 imp/s at approximately 100 mmHg PO2) and the response to hypoxia (22.4 +/- 1.6 vs. 32.3 +/- 1.2 imp/s at approximately 40 mmHg PO2, P < 0.05) in CHF rabbits. Ad CuZnSOD also normalized the blunted outward K+ current (IK) in CB glomus cells from CHF rabbits (369 +/- 14 vs. 565 +/- 31 pA/pF at +70 mV, P < 0.05). In addition, Ad CuZnSOD reduced the elevation of superoxide level in CBs from CHF rabbits. CONCLUSION: Downregulation of CuZnSOD in the CB contributes to the enhanced activity of CB chemoreceptors and chemoreflex function in CHF rabbits.
Authors: Yu-Long Li; Yi-Fan Li; Dongmei Liu; Kurtis G Cornish; Kaushik P Patel; Irving H Zucker; Keith M Channon; Harold D Schultz Journal: Circ Res Date: 2005-06-30 Impact factor: 17.367
Authors: P Ponikowski; T P Chua; M Piepoli; D Ondusova; K Webb-Peploe; D Harrington; S D Anker; M Volterrani; R Colombo; G Mazzuero; A Giordano; A J Coats Journal: Circulation Date: 1997-10-21 Impact factor: 29.690
Authors: Lie Gao; Wei Wang; Yu-Long Li; Harold D Schultz; Dongmei Liu; Kurtis G Cornish; Irving H Zucker Journal: Am J Physiol Heart Circ Physiol Date: 2005-01-06 Impact factor: 4.733
Authors: P Ponikowski; T P Chua; M Piepoli; W Banasiak; S D Anker; R Szelemej; W Molenda; K Wrabec; A Capucci; A J Coats Journal: Am J Cardiol Date: 1998-08-01 Impact factor: 2.778
Authors: Zhi-Yong Tan; Yongjun Lu; Carol A Whiteis; Annabel E Simms; Julian F R Paton; Mark W Chapleau; François M Abboud Journal: Circ Res Date: 2009-12-17 Impact factor: 17.367
Authors: Krupa Savalia; Devika S Manickam; Erin G Rosenbaugh; Jun Tian; Iman M Ahmad; Alexander V Kabanov; Matthew C Zimmerman Journal: Free Radic Biol Med Date: 2014-06-09 Impact factor: 7.376
Authors: Adil Z Solaiman; Robert P Feehan; Amy M Chabitnoy; Urs A Leuenberger; Kevin D Monahan Journal: Auton Neurosci Date: 2014-02-08 Impact factor: 3.145
Authors: Camilo Toledo; David C Andrade; Claudia Lucero; Alexis Arce-Alvarez; Hugo S Díaz; Valentín Aliaga; Harold D Schultz; Noah J Marcus; Mónica Manríquez; Marcelo Faúndez; Rodrigo Del Rio Journal: J Physiol Date: 2017-03-19 Impact factor: 5.182