The long term objectives of this study are to examine the role of alpha2- adrenoceptors in the control respiratory motor output and respiratory rhythm. The principal objective of the study is to determine the extent to which alpha2-adrenoceptors modulate respiratory rhythm, manifested as changes of efferent activity from medullary and spinal motoneurons to specific respiratory muscles. To carry out the specific aims of this proposal, the awake, standing goat model and the chloralose-anesthetized, artificially-ventilated goat model will be used to test specific hypotheses related to respiratory motor control by alpha2 adrenoceptors. Alpha-2 agonists (clonidine or guanabenz) induce respiratory arrhythmias in awake goats consisting of alternating periods of tachypneic breathing and respiratory depression. In anesthetized animals with bilateral vagotomy and peripheral chemoreceptors removed alpha2 agonists induce prolonged and variable apneas.
The specific aims of the proposed research are to, l) examine the role of vagal feedback in the development of breathing instabilities induced by alpha2-adrenoceptor agonists; 2) test the hypothesis that alpha2-adrenoceptors differentially control cranial and spinal motoneuronal activity; 3) examine the effects of central and peripheral (carotid body) chemosensory mechanisms on motoneuronal activation and their interactions with alpha2 adrenoceptors. Alpha-2 receptor agonists are important as adjuncts to gas anesthesia, analgesia, sedation and anti-hypertensive agents; however, there is little information available concerning the respiratory effects of these neuromodulating drugs. The data obtained by the proposed research will provide important information regarding our knowledge of the role of alpha2 adrenoceptors that have growing clinical significance in respiratory physiology.
