Functional Interaction Between Cardiac and Pulmonary Spinal Afferent Reflexes in Rats
Authors: Hahka Taija M. , Hong Juan , Xia Zhiqui , Lisco Steven J. , Zucker Irving H , Wang Han-Jun 
Published: April 2020

Studies from our laboratory and others have documented a potent sympathetic excitatory response triggered by cardiac spinal afferent activation (CSAR) in a variety of species including rodents, non‐human primates and dogs. In a recent study, we reported that activation of pulmonary spinal afferents by topical application of bradykinin (BK) on to lung surfaces evokes a similar sympatho‐excitatory reflex (PSAR). Our data further demonstrated that the sympatho‐excitatory responses to either CSAR or PSAR can be completely abolished by epidural application of resiniferatoxin (RTX) at the T1–T4 DRG levels, indicating that these afferents in heart and lung projects to similar spinal levels. However, it remains unclear whether CSAR and PSAR activation are synergistic or antagonistic when they are simultaneously stimulated. In the current study, we examined interaction between these two reflexes in urethane‐α‐chloralose anesthetized, vagotomized rats. We applied a square of filter paper (3 × 3 mm) saturated with BK (10 μg/ml) to lung surfaces to stimulate the PSAR alone. After BK was washed out, ~20 min was allowed to recover the sensitivity of pulmonary spinal afferents between applications. Subsequently, we applied left ventricular epicardial BK to activate the CSAR. Following CSAR activation, we activated the PSAR again to examine if the CSAR can further enhance the PSAR (i.e. cardiac‐pulmonary interaction). In a similar way, we examined if the PSAR could enhance the CSAR (pulmonary‐cardiac interaction). Our data (Table
1) show that either CSAR or PSAR activation alone evoked a potent sympatho‐excitatory response including increased blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA). However, we found that prior activation of the CSAR significantly inhibited the subsequent PSAR activation. Furthermore, removal of CSAR activation recovered the PSAR response. We observed an analgous inhibitory effect of the PSAR on the CSAR. Interestingly, the magnitude of the inhibitory effect of the CSAR on the PSAR appeared more pronounced than the effect of the PSAR on the CSAR. In control experiments, topical application of saline (vehicle) to the heart or lung did not affect the amplitude of the PSAR or CSAR activation respectively before and after saline (data not shown), suggesting that the functional inhibition between these two reflexes was not due to sensitivity loss caused by repeated chemical applications. In summary, our data suggest an inhibitory interaction between CSAR and PSAR. Future mechanistic work will be required to identify the potential interaction sites in their reflex arcs.

Support or Funding Information

National Heart, Lung, and Blood Institute (1R01HL121012 and 1R01HL126796).

Hemodynamic responses to PSAR before/after activation of the CSAR, and vice versa

PSAR

CSAR

Baseline

CSAR

Recovery

Baseline

PSAR

Recovery

ΔMAP (mmHg)

21.0±2.1

10.7±1.3
*

17.2±2.1

20.7±1.3

15.0±1.1
*

18.5±1.1

ΔHR (mmHg)

16.3±3.0

6.2±1.5
*

14.7±2.6

21.5±1.6

13.0±1.3
*

19.3±1.6

ΔRSNA (%baseline)

120.3±13.0

53.5±7.1
*

92.5±11.3

111.7±10.2

74.2±3.8
*

108.8±7.3

CSAR, cardiac spinal afferent reflex; HR, heart rate; MAP, mean arterial pressure; PSAR, pulmonary spinal afferent reflex; RSNA, renal sympathetic nerve activity. Mean±SE. n=6/each group;

*P<0.05 vs. baseline.