Previous studies in our laboratory have shown that progressive hypertension, with no consistent changes in heart rate, develops in dogs exposed for 15 days to avoidance conditioning and saline infusion. Typically, hypertension does not develop in dogs on avoidance schedules with normal sodium intake or in non-stressed, but salt-loaded dogs. The present project investigates physiological mechanisms presumed to participate in the pathogenesis of avoidance-saline hypertension. Studies involving direct monitoring of chronically-instrumented and behaviorally-trained dogs are designed to evaluate short-term and long-term changes in stroke volume, cardiac output, total peripheral resistance, renal blood flow and renal resistance. The role of the sympathetic nervous system in these cardiovascular adaptations will be assessed by measurements of plasma catecholamines and pharmacological blockade of adrenergic receptor activity. Changes in sodium balance and renal and adrenal hormones will be investigated by systematic analysis of blood and urine samples. The effects of increased calcium intake and calcium-entry blockade upon cardiovascular responses to avoidance and saline will also be evaluated. In addition, experiments are designed to test the hypothesis that behavioral interventions, such as dynamic exercise and biofeedback, which prevent peripheral vasoconstriction and reduction of renal functions between avoidance sessions will prevent the development of progressive hypertension. These experiments may elucidate pathophysiological mechanisms involved in long-term blood pressure control, and provide information on behavioral interventions useful for prevention or management of human essential hypertension.
