title: Intrathecal bombesin is sympathoexcitatory and pressor in rat.
abstract: Bombesin, a 14 amino-acid 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 μM 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.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Branimir
authors.initials: B
authors.lastname: Zogovic
authors.forename: Paul M
authors.initials: PM
authors.lastname: Pilowsky
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D001839:Bombesin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006935:Hypercapnia / Q000503:physiopathology; D018496:Hyperoxia / Q000503:physiopathology; D007263:Infusions, Parenteral; D008297:Male; D018377:Neurotransmitter Agents / Q000008:administration & dosage*; D009842:Oligopeptides / Q000494:pharmacology; D010791:Phrenic Nerve / Q000187:drug effects / Q000503:physiopathology; D012123:Pulmonary Ventilation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018004:Receptors, Bombesin / Q000187:drug effects / Q000378:metabolism; D013153:Splanchnic Nerves / Q000187:drug effects / Q000503:physiopathology; D013904:Thoracic Vertebrae; D013997:Time Factors; D014628:Vagotomy
chemical_list: D018377:Neurotransmitter Agents; D009842:Oligopeptides; D018004:Receptors, Bombesin; C061858:ICI 216140; D001839:Bombesin