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Hypertension in Rats Bearing an Adrenocorticotropic Hormone-, Growth Hormone-, and Prolactin-secreting Tumor (MtTF4)¹

Departments of Pathology [A. M., P. A. N., A. C. B.] and Biochemistry [J. L., A. C. B.], State University of New York at Buffalo, Buffalo, New York 14214

Blood pressure was measured in female Fischer F-344 rats implanted with MtTF4 tumor. Three different groups of animals were studied. Group 1 was given a normal diet and water as drinking fluid. Group 2 was fed a normal diet and given 1% sodium chloride solution as drinking fluid. Group 3 was uninephrectomized, fed a normal diet, and given 1% sodium chloride solution as drinking fluid. Body weight, food intake, and sodium intake were greater than controls in all 3 tumor-bearing groups. In Group 1, hypertension developed and was maximal by 6 weeks. In Group 2 (salt-drinking rats), hypertension was more severe, and its peak was reached at the 5th week. In Group 3 (salt-drinking, uninephrectomized rats), there was a sharp blood pressure increase as soon as the 2nd and 3rd week following tumor implantation. In all groups, the hypertension was transient, and about 1 week following the peak of hypertension the animals lost weight dramatically and died. This was particularly evident for the uninephrectomized rats drinking salt solution. Associated with the hypertension were hypernatremia, hypokalemia, and decreased content of renal renin. Kidneys of hypertensive rats were enlarged and pale and showed petechial hemorrhages on the surface. Cardiomegaly and necrotic lesions were present in their hearts, while the extremely enlarged adrenals showed tremendous vacuolization of the zona fasciculata, periodic acid-Schiff-positive colloid droplets, fat infiltration, and, especially in animals drinking salt solution, large areas of necrosis. Plasma levels of 11-deoxycorticosterone were very high in all groups of rats bearing the mammotropic pituitary hormone tumor. Adrenocorticotropic dysfunction due to the effects of the large amounts of adrenocorticotropic hormone secreted by the mammotropic pituitary hormone tumor appeared to be involved in the pathogenesis of the hypertensive cardiovascular disease seen in these animals. Hypertension failed to develop in adrenalectomized rats implanted with the tumor and receiving the daily dose of 1 mg of corticosterone s.c. A role for growth hormone or prolactin in the development of adrenocortical dysfunction cannot be excluded at this time.

¹ This investigation was supported by Research Grant HE 06975 from the National Heart and Lung Institute, NIH, Bethesda, Md.

Received 5/26/71. Accepted 8/25/71.