In Phase I of this award I will complete the research for my Ph.D. thesis in physiology investigating the autonomic regulation of tracheal smooth muscle in cats exposed to feline viral rhinotracheitis virus. A segment of trachealis muscle will be isolated in vivo and attached to a force transducer. The blood and nerve supply to the tracheal segment is maintained to allow local intra-arterial infusion of autonomic agonists and antagonists and the nerve supply is isolated for electrical stimulation. Two groups of cats will be studied. A principal group will be challenged by aerosol inhalation of feline viral rhinotracheitis virus, while a control group receives an aerosol of saline. Two days following challenge I will study autonomic regulation of the trachealis muscle. Muscarinic activity will be investigated by measuring the dose response to local intraarterial infusion of acetylcholine and the response to electrical stimulation of the vagus nerve with increasing stimulus frequency. Beta adrenergic activity will be investigated by examining the dose response to local infusion of isoproterenol and the response to stimulation of the cervical sympathetic nerves. Alpha1 and alpha2 adrenergic activity will be determined by the dose response to phenylephrine and clonidine, respectively. Stimulation of the vagus nerve after parasympathetic and sympathetic blockade will demonstrate the activity of the non-adrenergic inhibitory nervous system. Appropriate blockers will be used to determine specificity of responses. I will determine if viral effects are due to epithelial injury or inflammation by repeating the studies a) in cats in which tracheal epithelium is removed from the isolated tracheal segment, and b) in neutrophil-depleted cats. In Phase II I will conduct similar studies during recovery from the viral infection and study mechanisms of any changes in autonomic regulation observed in Phase I. Specific protocols for Phase II will be designed once the results of protocols of Phase I are available. I will repeat only the protocols which have identified abnormalities in autonomic regulation to define the time to determine the duration of these abnormalities following viral infection. Investigations of mechanisms will involve the use of specific blockers of arachidonic acid and metabolites. Airway reactivity in feline """"""""asthma"""""""" will also be studied.
| Killingsworth, C R; Paulauskis, J D; Shore, S A (1996) Substance P content and preprotachykinin gene-I mRNA expression in a rat model of chronic bronchitis. Am J Respir Cell Mol Biol 14:334-40 |
| Killingsworth, C R; Shore, S A (1995) Tachykinin receptors mediating contraction of guinea pig lung strips. Regul Pept 57:149-61 |
| Killingsworth, C R; Yu, M F; Robinson, N E (1992) Evidence for the absence of a functional role for muscarinic M2 inhibitory receptors in cat trachea in vivo: contrast with in vitro results. Br J Pharmacol 105:263-70 |
| Killingsworth, C R; Robinson, N E; Adams, T et al. (1990) Cholinergic reactivity of tracheal smooth muscle after infection with feline herpesvirus I. J Appl Physiol 69:1953-60 |
