proscillaridin and Hypertension

Endogenous digitalis-like factors in humans are presumably cardenolides and bufadienolides. To test whether bufadienolide-like substances may circulate in human blood, we used antibodies from rabbits against the bufadienolide proscillaridin A to measure the concentration of cross-reacting material in human plasma with an indirect enzyme-linked immunosorbent assay. IgG had an apparent affinity of 2 x 10(-9) mol/L for proscillaridin A. It was specific for bufadienolides and did not cross-react with cardenolides or several steroid hormones. Extraction of human plasma with ethanol and fractionation of this extract over a high-performance liquid chromatographic reverse-phase C18 column with a propanol/isopropanol gradient resulted in the separation of three peaks of increasing hydrophobicity (ED1, ED2, ED3) that inhibited the sodium pump of human red blood cells and cross-reacted with proscillaridin A antibodies. The concentration of the proscillaridin A immunoreactivity ED1 in normotensive subjects had a geometric mean of 0.1 nmol/L, with a dispersion factor of 8.77. ED1 correlated positively in a group of 60 normotensive subjects, 22 patients with hypertension, and 19 patients with chronic renal failure with mean arterial blood pressure (log ED1 [nmol/L] = 0.013 x mm Hg-2.17, r = .25, P < .05), systolic pressure (log ED1 [nmol/L] = 0.010 x mm Hg-2.23, r = .32, P < .01), and pulse pressure (log ED1 [nmol/L] = 0.019 x mm Hg-1.80, r = .38, P < .0001). There was no correlation with other parameters of the donors. We conclude that several substances cross-reacting with proscillaridin A antibodies and inhibiting the sodium pump of human red blood cells circulate in human blood. The level of one of these substances (ED1) correlates with mean arterial and pulse pressures.

Topics: Adult; Animals; Blood Pressure; Bufanolides; Cholenes; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Proscillaridin; Rabbits; Reference Values; Systole

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.

Topics: Animals; Antibodies; Blood Pressure; Body Weight; Digoxin; Hypertension; Proscillaridin; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vaccination

The effect of an association of proscillaridin A, thioridazine and Cori ester in ambulatory management of certain heart diseases, particularly in aged subjects, was assessed. Satisfactory results were observed in 58.3% of cases, with significant improvement of cardiac erethism, psychomotor instability and sleep disturbances, as well as cardiac frequency and signs of myocardial insufficiency. It is felt that the association is of assistance in the treatment of certain heart diseases unaccompanied by frank signs of insufficiency, especially in aged subjects.

Topics: Aged; Bufanolides; Coronary Disease; Drug Combinations; Female; Glucosephosphates; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Male; Middle Aged; Proscillaridin; Pulmonary Heart Disease; Thioridazine

Topics: Angina Pectoris; Arteriosclerosis; Asthma; Cardiac Glycosides; Drug Therapy; Electrocardiography; Geriatrics; Heart Failure; Hypertension; Proscillaridin