Chronic exposure of rats to cold (5-6 degree C.) induces hypertension, which is characterized by an increase in systolic, diastolic, and mean blood pressures, as well as cardiac (left ventricular) hypertrophy. This is an important finding since it represents for the first time a """"""""naturally occurring"""""""" hypertension which is induced without surgical intervention; administration of excessive doses of hormones or drugs, or generic manipulation. The overall objective of this proposal is to assess potential mechanisms that may contribute to the development of cold-induced hypertension. One possibility relates to the fact that cold-treated rats ingest excessive amounts of NaC1 as a result of an obligatory increase in food intake.
The aim of the first experiment is to investigate this possibility. A further possibility relates to the mediation of the renin-angiotensin-aldosterone (RAA) system in the induction of hypertension during exposure to cold. It is postulated that increased activity of the RAA system, coupled with ingestion of excessive amounts of NaC1, result in the induction of a mineralocorticoid-type of hypertension. Therefore, the aim of an additional experiment is to test the effect of chronic blockade of the angiotensin I converting enzyme by captopril on the development of cold-induced hypertension, as well as its rate of return to control level after removal from cold. A further aim is to assess changes that may occur in various components of the RAA system during chronic exposure to cold, including plasma renin activity, plasma aldosterone and renin contractions mRNA for renin substrate in several tissues, vascular responsiveness to exogenous administration of angiotensin II, and the regulation of receptors for angiotensin II and the regulation of receptors for angiotensin II in brain and other tissues. In addition, it is the aim of a further study to assess whether a change in baroreceptor function precedes, or results from, the development of hypertension during exposure to cold. Changes in the regulation of alpha1 - and alpha2 -adrenoceptors in the brain will also be assessed during exposure to cold because of their potential involvement in the development of hypertension. Finally, the possibility that intermittent exposure to cold can induce hypertension will be tested.
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