Intrathecal bombesin is sympathoexcitatory and pressor in rat

Branimir Zogovic, Paul M. Pilowsky

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Abstract

Bombesin, a 14 aminoacid peptide, is pressor when administered intravenously in rat and pressor and sympathoexcitatory when applied intracerebroventricularly. To determine the spinal effects of bombesin, the peptide was administered acutely in the intrathecal space at around thoracic spinal cord level six of urethane-anesthetized, paralyzed, and bilaterally vagotomized rats. Blood pressure, heart rate, splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, and end-tidal CO 2 were monitored to evaluate changes in the cardiorespiratory systems. Bombesin elicited a long-lasting excitation of sSNA associated with an increase in blood pressure and tachycardia. There was a mean increase in arterial blood pressure of 52 ± 5 mmHg (300 μM; P < 0.01). Heart rate and sSNA also increased by 40 ± 4 beats/min (P < 0.01) and 162 ± 33% (P < 0.01), respectively. Phrenic nerve amplitude (PNamp, 73 ± 8%, P < 0.01) and phrenic expiratory period (+0.16 ± 0.02 s, P < 0.05) increased following 300 μ M bombesin. The gain of the sympathetic baroreflex increased from -2.8 ± 0.7 to -5.4 ± 0.9% (P < 0.01), whereas the sSNA range was increased by 99 ± 26% (P < 0.01). During hyperoxic hypercapnia (10% CO 2 in O 2, 90 s), bombesin potentiated the responses in heart rate (-25 ± 5 beats/min, P < 0.01) and sSNA (+136 ± 29%, P < 0.001) but reduced PNamp (from 58 ± 6 to 39 ± 7%, P < 0.05). Finally, ICI-216,140 (1 mM), an in vivo antagonist for the bombesin receptor 2, attenuated the effects of 300 μM bombesin on blood pressure (21 ± 7 mmHg, P < 0.01). We conclude that bombesin is sympathoexcitatory at thoracic spinal segments. The effect on phrenic nerve activity may the result of spinobulbar pathways and activation of local motoneuronal pools.

Original languageEnglish
Pages (from-to)R1486–R1494
Number of pages9
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume301
Issue number5
DOIs
Publication statusPublished - Nov 2011

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Keywords

  • Baroreflex
  • Blood pressure
  • Heart rate
  • Phrenic nerve activity
  • Splanchnic sympathetic nerve activity

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