Effects of ricin administration to rabbits on the ability of their coronary arteries to contract and relax in vitro.
We have previously shown that ricin, a toxic lectin from the castor bean, increases cardiac output and blood flow to the heart in rabbits in the early stage of its intoxication and causes hemorrhage and necrosis in the heart following a lethal dose. To investigate possible alterations in coronary arteries following ricin administration, their responses to serotonin (5-HT), histamine, norepinephrine (NE), and acetylcholine (ACh) were determined. Rabbits were given 0.22 microgram/kg of ricin i.v. and euthanized 48 hr later. Cumulative contractions of rabbit coronary artery rings to 5-HT and histamine were measured. Cumulative relaxations to ACh and NE were measured in rings contracted with the histamine H1 receptor agonist 2-(2-aminoethyl)pyridine. Ricin significantly increased the EC50s of contractions of rabbit coronary artery rings to 5-HT and histamine. Maximal contractions to most agonists tested were increased. The EC50 of relaxation of rabbit coronary artery to NE was decreased, although the maximal relaxations to ACh and NE were not increased to a significant extent. It is likely that in the early stage of ricin intoxication in rabbits the sum of the effects of these vasoactive agents is to reduce the vascular tone of the coronary artery and thus reduce blood pressure and, in the late stage of ricin intoxication, vasospasm of coronary artery may cause micro- and macrocirculatory collapse.
Zhang
L
L
College of Pharmacy, University of Oklahoma, Oklahoma City 73190.
Hsu
C H
CH
Robinson
C P
CP
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D012276:Ricin / Q000633:toxicity*; D012701:Serotonin / Q000494:pharmacology
D017442:Histamine Agonists; D011725:Pyridines; D012701:Serotonin; D006632:Histamine; D012276:Ricin; C006183:2-(2-aminoethyl)pyridine; D000109:Acetylcholine; D009638:Norepinephrine