Ricin is a toxic lectin from the castor bean. The time course of its toxic effects on the cardiovascular system of rabbits was investigated after determining its LD50 and minimum lethal dose in rabbits by the Up and Down method, as a basis for dosing. Systolic and diastolic arterial pressures, electrocardiogram and heart rate were recorded for 48 hr following administration of either a toxic sublethal (0.22 microgram/kg) or minimum lethal dose (0.44 microgram/kg) of ricin. After a delayed onset of about 20 hr, the minimum lethal dose (0.44 microgram/kg) of ricin caused a significant decrease in both systolic and diastolic pressures (P < 0.05). The systolic and diastolic pressures decreased 0.47 and 0.39 mmHg/hr more so than control groups, respectively. A toxic sublethal dose (0.22 microgram/kg) of ricin did not significantly alter either systolic or diastolic pressure. Neither dose of ricin caused cardiac arrhythmias or significantly increased heart rate. We conclude that the lethal hypotensive sequelae of ricin toxicity in the rabbit were peripheral in origin and not cardiogenic at these two doses.
Ricin, a toxic lectin from the castor bean, affects the cardiovascular system. Because calcium is very important in cardiotoxicity and cell intoxication, we studied the effects of ricin pretreatment to rabbits on basal intracellular calcium levels and calcium uptake and release from isolated papillary muscle, microsomes, and mitochondria. An increase in basal intracellular calcium levels was observed. Ricin pretreatment nearly doubled the intracellular-free Ca2+ concentration as measured by fura-2 fluorescence microscopy in isolated myocytes (p = 0.002). Ricin did not alter basal calcium efflux in isolated papillary muscles. However, ricin inhibited the NE-induced calcium efflux (expressed as fractional efflux ratios) in papillary muscles from rabbits receiving the minimum lethal dose of ricin at 25-35 minutes (p = 0.002 and 0.003, respectively). Ricin depressed basal calcium uptake into isolated papillary muscles at 5 minutes (mean +/- SEM, mumol/g wet weight) (control: 3.68 +/- 0.57; ricin: 2.31 +/- 0.28, p = 0.045, n = 6). Ricin pretreatment significantly depressed calcium uptake into microsomes (mean +/- SEM, mumol/g protein) (control: 9.9 +/- 1.9; ricin: 3.1 +/- 1.9, p = 0.025, n = 6). Calcium uptake into mitochondria was increased at the beginning (2 minutes, p = 0.048), but not thereafter. Thus, administration of ricin disturbed calcium homeostasis in the rabbit heart, which may be at least partially responsible for altering cardiac function and myocardial cell death.
Ricin, a toxic lectin from castor beans, reduces blood pressure. The current studies determined the effect of ricin on contractions in response to norepinephrine (NE) of rabbit central ear artery, endothelium-dependent relaxations to methacholine and ATP of aorta rings and endothelium-independent relaxations to papaverine in central ear artery and aorta rings. Rabbits were given 0.11 or 0.22 micrograms kg-1 ricin i.v. and 18 h, 4 days, or 7 days later the arteries were removed and tested. Maximal contractions to NE were increased by 8-23% (P > 0.05) with ricin treatment. The EC50 was increased in five of six ricin-treated groups, although only significantly so at 18 h after a minimum lethal dose of ricin. Maximum relaxations to methacholine were increased by 20-57% (P > 0.05) at 18 h following both ricin doses but returned to control values at later time points. Relaxations in response to ATP were significantly enhanced in all ricin-treated groups (95-205%) except in the 18 h and 4-day 0.11 microgram kg-1 dose groups where the increase was 0-46%. Relaxations in response to papaverine were not altered in either artery. Thus, ricin decreases the sensitivity of the rabbit central ear artery to NE and increases endothelial-dependent relaxations of the rabbit aorta. Therefore, decreased blood pressure following ricin administration may be due to vasodilation caused by decreased vascular contractions and increased endothelial-dependent vascular relaxation.
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