Compensatory mechanisms to maintain blood pressure in paraplegic rats: implication of central tachykinin NK-1 and NK-3 receptors?

Abstract

People with high level spinal cord injury (SCI) suffer from both hypotension and spontaneous hypertension due to loss of supraspinal control of spinal sympathetic outflow. Few reports have addressed whether any changes occur in central regulation of blood pressure (BP) and heart rat (HR) at the supraspinal level. Central tachykinin NK-1 and NK-3 receptors are located in many cardiovascular areas in the brain and are known to modulate BP and HR. This study examined the intracerebroventricular (i.c.v.) effects of the selective NK-1 receptor agonist [Sar(9), Met(O(2))(11)]SP (65pmol, n=6) and NK-3 receptor agonist senktide (650pmol, n=6) on mean arterial pressure (MAP) and HR before and after complete spinal cord transection at thoracic level 4 (T4). [Sar(9), Met(O(2))(11)]SP evoked increases in MAP and HR which were still present 4days after the T4 SCI. Further analysis using the beta(1)-adrenoceptor antagonist atenolol (10mgkg(-1)) revealed an increased contribution of HR in the MAP increase after SCI. For senktide, 2 and 5weeks after T4 SCI, the rise in MAP induced by senktide was significantly increased in magnitude and was similar to a normal response at 8weeks. These effects were accompanied by a bradycardia, which was still present and amplified at 8weeks. Our results reveal a transient potentiation of the senktide-mediated MAP effect and a greater contribution of the HR in MAP increase by [Sar(9), Met(O(2))(11)]SP in T4 transected rats. Although the significance of these changes remains to be established. This suggest a reorganization of supraspinal mechanisms regulating BP and HR after a high level SCI. Central NK-1 and NK-3 receptors might therefore contribute to the maintenance of MAP following high thoracic SCI.

• Authors: Frank Cloutier, Jenny L Lauschke, Pascal Carrive
• Journal: Neuropeptides (Neuropeptides) Vol. 44 Issue 2 Pg. 199-207 (Apr 2010) ISSN: 1532-2785 [Electronic] Netherlands
• PMID: 20096457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antihypertensive Agents
• Receptors, Neurokinin-1
• Receptors, Neurokinin-3
• Atenolol

Topics

• Analysis of Variance
• Animals
• Antihypertensive Agents (pharmacology)
• Atenolol (pharmacology)
• Behavior, Animal (drug effects)
• Blood Pressure (drug effects, physiology)
• Brain (drug effects, metabolism)
• Heart Rate (drug effects, physiology)
• Male
• Paraplegia (metabolism)
• Rats
• Receptors, Neurokinin-1 (agonists, metabolism)
• Receptors, Neurokinin-3 (agonists, metabolism)
• Spinal Cord Injuries (metabolism)
• Thoracic Vertebrae