Activation of arterial baroreceptors is thought to occur as a result of an increase of arterial pressure via direct mechanical deformation and strain of the nerve ending when the vascular wall is stretched. Arterial baroreceptors and baroreflexes play an important role as both short-and long-term regulators of arterial blood pressure. There have been a number of difficulties in the study of arterial baroreceptors. It is not possible to measure the strain or deformation of the nerve ending itself since a coupling exists between the mechanical elements (vascular wall) and the neural elements responsible for the transduction process. The relation between the receptor potential and activation of the spike- initiating region leading to the generation of action potential may not be fixed or constant. The receptor potential of baroreceptors in vivo or in situ is very difficult to measure. Thus, the events which link arterial pressure to afferent nerve discharge reflect a fundamental limitation in our attempt to understand the basic mechanisms of baroreceptor activation and modulation. The long-term objective of the proposed research project is to define the signal transduction pathways involved in the activation of baroreceptor neurons at the cellular level by determining single channel activity and whole-cell responses in baroreceptor neurons in response to stretch in vitro. Two experimental approaches will be used: direct electrophysiological measurement of single channel behavior and whole- cell conductances, and measurement of intracellular calcium in rat baroreceptor neurons in vitro. The first specific aim is to determine whether mechano-electrical transduction of baroreceptor neurons is mediated via stretch-activated channels. The biophysical properties of these channels will be determined. The second specific aim is to determine the signal- transduction pathways of baroreceptor neurons in response to mechanical stimulation. The whole-cell properties of the different baroreceptor neuronal types will be determined as well as the role of an intracellular calcium rise following mechanical stimulation.
The third aim i s to determine whether the mechano-electrical transduction process can be modulated by humoral agents known to affect arterial baroreceptors at both the single channel and whole-cell level. The roles of different potassium conductances on baroreceptor behavior and the effects of putative modulators on single channel and whole-cell conductances will be investigated. The results from these studies will allow insight into the basic mechanisms of baroreceptor activation and modulation and define the significance of the integrating capacity of the baroreceptor. These findings may have important implications pertaining to hypertension and other cardiovascular diseases where aberrant baroreceptor and baroreflex behavior has been observed.
| Ryan, Michael J; Liu, Beiying; Herbowy, Michael T et al. (2003) Intercellular communication between renin expressing As4.1 cells, endothelial cells and smooth muscle cells. Life Sci 72:1289-301 |
| Ryan, M J; Black, T A; Gross, K W et al. (2000) Cyclic mechanical distension regulates renin gene transcription in As4.1 cells. Am J Physiol Endocrinol Metab 279:E830-7 |
| Calvo, W J; Hajduczok, G; Russell, J A et al. (1999) Inhibition of nitric oxide but not prostacyclin prevents poststenotic dilatation in rabbit femoral artery. Circulation 99:1069-76 |
