PEPTIDERGIC MODULATION OF SYMPATHETIC COTRANSMISSION

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The proposed research during the fellowship will provide me with vital experience of sympathetic nervous system activity studies. Thus, my main goals for this period are: (i) To study the modulating effects of cardiovascular peptides ET, ANP, and BNP on the pre- and postsynaptic mechanisms of peripheral sympathetic cotransmission at the levels of isolated tissues in vitro and of an organism devoided of central reflexes in vivo as well as to study the participation of the endothelium, the EDRF/NO, cGMP, IP3, and Ca++ in these effects; (ii) To learn the basic techniques necessary for studies on peripheral sympathetic cotransmission, particularly those related to a) transmitter (ATP and NE) release measurement, b) contractile responses in isolated blood vessels, c) intracellular Ca++ and cyclic nucleotide signaling and d) hemodynamics of pitched animals (see Item 21, Research plan). Professor Westfall's laboratory is an ideal place to study the role of endogenous peptides on sympathetic neurotransmission. Professor David Westfall and his group have played a fundamental role in developing the concept that sympathetic neurotransmission involves the release of the cotransmitters ATP and NE. In addition his group has recently developed the concept that prejunctional purinoceptors, which modulate neurotransmitter release, may exist as several subtype. The laboratory is also well known for its ability to develop new methodologies to apply to issues of neurotransmission. For example, his laboratory is one of the few in the world where the release of ATP and NE can be simultaneously evaluated. The opportunity to learn and work in such an environment particularly in a place where the research interests are so congruent with my own, will no doubt enhance the development of my scientific career.