Hypoxia‐induced Sighs Correlate with High Amplitude Bursts in Splanchnic (S), but not Renal (R) or Lumbar (L), Sympathetic Nerve Activity (SNA): Role of Bombesin‐Like Peptides in the PreBotzinger Complex

Abstract

Previous experiments in inactin anesthetized (100 mg/kg, i.v.) spontaneously breathing male SD rats found that hypoxia (HX, O2 saturation ~ 50%) increased frequency(F) and amplitude (amp) of phrenic (Ph) nerve activity (NA) during eupnea, but distribution of SSNA across eupneic Ph cycles was similar for normoxia and HX [inspiration (I1, I2) > expiration (E1, E2)]. HX produced high amp bursts in PhNA (~ 4 to 6/min), followed by brief apnea (sighs). Correlation analysis during sighs revealed that SSNA redistributed such that high amplitude bursts in SSNA occurred in late inspiration (I2 > I1, E1, E2). In current experiments RSNA (n = 6) and LSNA (n = 3) were correlated with PhNA during HX. During eupnea RSNA was greater in late expiration compared to late inspiration (E2 > I2) with a similar trend for LSNA. HX produced PhNA sighs, but neither RSNA nor LSNA preferentially correlated with phases of the Ph cycle. In the PreBotzinger Complex (PreBot) 2 bombesin‐like peptides (Bom), neuromedin B (NMB) and gastrin‐releasing peptide (GRP), generate sighs (Li et. al., 2016). We evaluated the role of NMB and GRP in the Pre‐Bot in redistribution of SSNA during sighs. PhNA and SSNA were correlated before and after bilateral microinjections (100 nl) into the PreBot of a Bom receptor agonist cocktail [Bom‐agonists) in rats breathing 100% O2 (n = 3). Bom‐agonists increased Ph amp and F during eupnea, but the distribution of SSNA across the eupneic Ph cycle was similar before and after PreBot Bom‐agonists (I1, I2 > E1, E2). Bom‐agonists produced high amp bursts in PhNA (131% of eupneic; 4.6 ± 0.5/min) with prolonged expiration (0.90 ± 0.08 vs 0.74 ± 0.07 sec), indicative of sighs. However, unlike sighs due to HX, with PreBot Bom‐agonists while rats breathed 100% O2, the distribution of SSNA across the Ph cycle was similar for sighs and eupnea (I1, I2 > E1, E2). In separate rats (n = 4), a cocktail of Bom‐antagonists was injected bilaterally (100 nl) into the PreBot (PreBot‐bX) during HX. PreBot‐bX decreased the number (2.6 ± 0.3 vs 1.4 ± 0.4/min) and amplitude (P= 0.08) of PhNA sighs. Correlation of SSNA across the Ph cycle was not changed by preBot‐bX during eupnea (I1, I2 > E1, E2), but HX‐induced redistribution of SSNA during sighs (I2 > E1, E2) was eliminated by PreBot‐bX. Thus, Bom‐like peptides in the PreBot contribute to sighs, but correlation of sighs with high amp bursts in SSNA was evident only with HX‐induced sighs. Based on these results and our previous finding that inhibition of the paraventricular nucleus of the hypothalamus (PVN) resulted in uncoupling of SSNA with inspiratory sighs, we speculate that HX activates descending projections from the PVN which modulate cardiorespiratory coupling in the medulla during sighs.Support or Funding InformationNIH R01 HL98602This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.