Inhibition by Salmon Calcitonin (SCT) of Desoxycorticosterone Acetate (DOCA) Induced Hypertension in the Rat

Abstract

We have previously reported the capability of SCT to produce an acute diuresis and natriuresis in the saline loaded rat (1), as well as its ability to reduce the paw edema or inflammatory phase associated with the chronic disease state known as rat adjuvant arthritis (12). In addition, we have noted a significant decrease in the heart weight of normal rats given high doses of salmon calcitonin for 7 days (unpublished). We thus became interested in determining what effects SCT might have in a chronic hypertensive state such as that produced in rats by administration of DOCA in combination with a high salt intake. Methods. Two separate experiments were performed in which female Sprague-Dawley rats with initial weights of 50–70 g were treated sc for 5 weeks with 5 or 25 mg/kg/ dose of DOCA given b.i.d. with 1% NaCl in the drinking water. Synthetic salmon calcitonin (4000 MRC u/mg), purified porcine calcitonin (100 MRC u/mg), or synthetic human calcitonin (80 MRC u/mg) was administered sc at a dosage of 5 MRC u/kg/ dose b.i.d. in a 16% gelatin vehicle concomitantly with DOCA but at a different injection site. At the end of the treatment period direct measurements of aortic blood pressure were recorded in the unanesthetized state over at least a 5-min period following cannula insertion and pressure stabilization. Systolic, diastolic, mean blood pressure, and heart rate were recorded. The animals were then sacrificed and measurements made of heart and kidney weights. Appropriate control groups receiving distilled water or 1% NaCl to drink and injected with vehicle were included. Levels of statistical significance for group differences were determined using Student's t test. Results. In Table I are shown the results of the blood pressure measurements in the two experiments after 5 weeks of treatment.