The objectives of this Project are to utilize a new airpuff stress phenotype to elucidate the neural substrates, pharmacology and genetic basis of abnormal cardiovascular responses to mild stressful stimuli in the Spontaneously Hypertensive Rat (SHR) and to define the usefulness of this new phenotype to an understanding of the etiology of genetic hypertension in rodents and man. The phenotype utilizes an airpuff startle stimulus which elicits a classical startle reaction accompanied by a complex cardiovascular response. The genetic hypertensive rat exhibits aberrant and excessive cardiovascular responses to the stimulus. Central to the studies proposed are recent results demonstrating that the airpuff stimulus activates expression of immunoreactive fos in a subset of brain nuclei in the hypothalamus, midbrain and brainstem in a startle-, strain- and habituation-dependent manner, with greater activation in SHR brain nuclei. Studies will define fos expression in prehypertensive rats, evaluate the effects of the baroreceptor reflex on fos expression and compare brain and spinal fos expression. Double-labeling studies of fos and selected brain receptor systems will probe the pharmacology of responding neurons. Receptor blockade will test the function of double- labeled neurons in target nuclei. In addition, genetic studies of the new phenotype will employ the set of Recombinant Inbred Rat strains. The results of these studies should enhance our knowledge of the role of environmental stress on the etiology of hypertension and related cardiovascular disorders.
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