The spontaneously hypertensive rat (SHR) and its control strain, the Wistar-Kyoto rat (WKY), have been studied extensively as a model for genetic hypertension. SHRs have higher blood pressures (BP) than WKYs, are more hyperactive, react more to stress, and have less ability to habituate. SHRs also have less responsive vasopressin (AVP) and oxytocin (OT) systems. These differences in SHRs may not be associated with the hypertension trait. Two new rat strains, the Wistar-Kyoto Hypertensive (WKHT) and the Wistar-Kyoto Hyperactive (WKHA), have been developed to clarify the relationships among blood pressure (BP), behavioral characteristics, and neurohormones thought to be involved in BP regulation. The WKHA is genetically hyperactive and not hypertensive, and the WKHT is genetically hypertensive, without being hyperactive. These new strains can assist in determining the behavioral and peptide characteristics of the SHR related to hypertension. Since both AVP and OT have been shown to affect BP and behavior, these systems may be major contributors to hypertension in the SHR and WKHT. To investigate whether these peptides are secreted differently in hypertensive and hyperactive models, hypertonic stimuli (HS) which increase BP will be injected centrally and peripherally to determine which models exhibit altered central and peripheral AVP and OT levels and/or behavior. This challenge will occur with and without an accompanying AVP antagonist to further clarify the role of AVP. Sympathetic arousal will be assessed by plasma adrenocorticotropic hormone (ACTH) levels. A second pressor stimulus, Angiotensin II (AII), which is thought to operate via different mechanisms than HS, will be administered to compare its role in AVP, OT, ACTH production and BP alteration with HS. All rats will be implanted with intracerebroventricular push-pull cannulas (for sampling CSF while simultaneously injecting HS) and with femoral (for BP and heart rate measurement) and jugular (for plasma sampling) catheters. After recovery AVP, OT and ACTH changes in cerebrospinal fluid and plasma will be determined before, during and after the administration of the stimuli into the third ventricle. HS or AII will be administered centrally and peripherally, with and without the vasopressin antagonist, while collecting CSF and plasma and monitoring BP and heart rate. Behavior will be recorded to the same stimuli in freely moving, conscious animals in the home cage. Data will be analyzed by split-plot ANOVAs, post hoc tests, correlation and graphically. Students will be trained in all phases of the project.
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