Role of endogenous cardiac glycosides in the spontaneously hypertensive rat—antagonism by active immunization

Abstract

The effects of simultaneous active immunization against two cardiac glycoside drugs, digoxin and proscillaridin, have been examined in young spontaneously hypertensive and Wistar-Kyoto rats. Control animals were immunized with protein carrier only. Animals were studied from 5 weeks to 13 weeks of age. Effectiveness of immunization to produce antibody responses was assessed at the end of the study by estimating the titer of antibodies in plasma against both of the antigens. Robust antibody responses were obtained. Immunization had no effect on the normal growth of these animals. Further, immunization against cardiac glycosides did not change blood pressure in either strain of animals. Blood pressure in the SHR increased as anticipated as the weanling animals grew to maturity. These studies indicate that active immunization against cardiac glycosides does not alter blood pressure in the SHR in spite of strong evidence for increased levels of endogenous cardiac glycosides in this strain.

Mammalian Bufadienolide Is Synthesized From Cholesterol in the Adrenal Cortex by a Pathway That Is Independent of Cholesterol Side-Chain Cleavage

“…10,11 However, the identity, origin, and biosynthetic pathways of these compounds in mammals remains to be fully understood. Analogous to phytoestrogens, some studies suggest that the diet may be a source of such material in plasma and urine, [12][13][14][15][16][17][18] whereas others have proposed that the hypothalamus, 19 -21 placenta, 5,22 or adrenal cortex [23][24][25] may be the source of the endogenous circulating Na ϩ pump inhibitor. We have demonstrated that Y-1 murine tumor AC cells grown in defined serum-free conditions produce a material that shows important similarities to MBG.…”