nNOS gene transfer to the carotid body decreased baseline discharge (4.5 vs 7.3 imp/s) and response to hypoxia (18.3 vs 35.6 imp/s) from chemoreceptors in heart failure rabbits (P<0.05).
Does nNOS gene transfer to the carotid body reduce enhanced chemoreceptor activity in chronic heart failure rabbits?
Gene transfer of nNOS to the carotid body reverses enhanced chemoreceptor activity and blunts renal sympathetic nerve activity in a rabbit model of heart failure.
Absolute Event Rate: 4.5% vs 7.3%
p-value: p=<0.05
Our previous studies showed that decreased nitric oxide (NO) production enhanced carotid body (CB) chemoreceptor activity in chronic heart failure (CHF) rabbits. In the present study, we investigated the effects of neuronal NO synthase (nNOS) gene transfer on CB chemoreceptor activity in CHF rabbits. The nNOS protein expression and NO production were suppressed in CBs (P<0.05) of CHF rabbits, but were increased 3 days after application of an adenovirus expressing nNOS (Ad.nNOS) to the CB. As a control, nNOS and NO levels in CHF CBs were not affected by Ad.EGFP. Baseline single-fiber discharge during normoxia and the response to hypoxia were enhanced (P<0.05) from CB chemoreceptors in CHF versus sham rabbits. Ad.nNOS decreased the baseline discharge (4.5+/-0.3 versus 7.3+/-0.4 imp/s at 105+/-1.9 mm Hg) and the response to hypoxia (18.3+/-1.2 imp/s versus 35.6+/-1.1 at 40+/-2.1 mm Hg) from CB chemoreceptors in CHF rabbits (Ad.nNOS CB versus contralateral noninfected CB respectively, P<0.05). A specific nNOS inhibitor, S-Methyl-L-thiocitrulline (SMTC), fully inhibited the effect of Ad.nNOS on the enhanced CB activity in CHF rabbits. In addition, nNOS gene transfer to the CBs also significantly blunted the baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in CHF rabbits (P<0.05). These results indicate that decreased endogenous nNOS activity in the CB plays an important role in the enhanced activity of the CB chemoreceptors and peripheral chemoreflex function in CHF rabbits.
Li et al. (Sat,) conducted a other in chronic heart failure (CHF). neuronal NO synthase (nNOS) gene transfer (Ad.nNOS) vs. contralateral noninfected CB / Ad.EGFP was evaluated on baseline single-fiber discharge from CB chemoreceptors (p=<0.05). nNOS gene transfer to the carotid body decreased baseline discharge (4.5 vs 7.3 imp/s) and response to hypoxia (18.3 vs 35.6 imp/s) from chemoreceptors in heart failure rabbits (P<0.05).
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