SODIUM & NEUROPEPTIDES IN STRESS INDUCED HYPERTENSION

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Stress and sodium are factors linked to the pathogenesis of hypertension. These two factors, stress and sodium, are also interrelated with the opiate and angiotensin systems. Substantial evidence is available supporting a role for these substances in hypertension of differing etiologies. However, there has not been a comprehensive study of these factors combined in stress induced hypertension. This study is designed to investigate the mechanism(s) responsible for elevations in blood pressure due to stress and sodium. The development of miniature pulsed Doppler flow probes has made it possible to obtain data concerning hemodynamic variables in conscious rats that until now was only possible in larger animals. As a result of these technological advances it is now possible to study cardiovascular correlates in establish rat models of stress. Fully instrumented conscious Wistar rats will be used to obtain data concerning the hemodynamic status (blood pressure, cardiac output, total peripheral resistance) as well as baroreceptor sensitivity in three models of stress (territorial stress, rotation stress and isolation stress) while being exposed to three dietary sodium regimes (low, normal, high sodium). Coupled with this data, certain rats will be similarly tested under the above experimental conditions while chronically blocking the angiotensin (sarthran, converting enzyme inhibitor) or opiate (naloxone) systems via osmotic minipump infusions. Whether the action, if any, of these peptides is peripheral or central will also be examined using either central administration techniques or substances that do not cross the blood brain barrier. Interactions between stress and sodium and the relationships with neuropeptidergic systems known to participate in cardiovascular control will be evaluated. The defense reaction, even if only slightly activated when alerted, is a major influence on blood pressure regulatory mechanisms. It is likely that interactions and influences of angiotensin II, opiates and sodium with stress is an occurrence of normal daily life. The studies proposed within this application will provide missing information concerning these important interactions and their role in blood pressure regulation. Elucidating these underlying mechanisms can provide a basis to reverse or prevent the deleterious actions of stress and sodium which are encountered daily.