Within 3 weeks of mild cold exposure (5 degrees C), rats develop hypertension, including cardiac hypertrophy. This appears to be the only known natural form of experimentally-induced hypertension, requiring no surgery, drugs, hormones, or genetic manipulation. The objective of this proposal is to determine mechanisms that may contribute to the development and maintenance of this cold-induced hypertension. For this, cardiac output and contractility, stroke volume, right atrial pressure, total peripheral resistance, resistance of the hind quarters to blood flow, vascular reactivity, as well as changes in the structural characteristics of mesenteric resistance vessels will be measured at 1, 3, and 5 weeks of exposure to cold to assess the role of each in cold- induced hypertension. Since the renin-angiotensin system is important in the development of this hypertension, changes in plasma renin activity, the activity of the angiotensin I converting enzyme, the regulation of AngII receptors, mRNA for angiotensinogen, mRNA for ANGII, AT-1 receptors in various tissues will be measured after 1, 3, and 5 weeks of cold. Other studies will assess the areas of appearance and intensity of response of the oncogene, cfos, in the brain and adrenals of cold-treated rats after iv infusion of AngII. This will identify responding areas as well as the intensity of the response compared to warm-controls. cfos response will also be correlated with the location of AngII receptors. In addition, the effects of exposure to cold on fluid and electrolyte exchanges, ECF and plasma volumes, and renal responsiveness to pitressin and aldosterone will be measured at graded intervals to assess their roles in cold-induced hypertension.
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