Characterization and mechanisms of the cardiovascular and haemodynamic alterations induced by scorpion venom in rats.
The scope of this work was to investigate the nature, chronology and mechanisms of the cardiovascular disorders induced by scorpion envenomation. Anaesthetized rats were instrumented for measurement of cardiac output (CO), renal (RBF) and muscular (HBF) blood flows (pulsed Doppler flowmetry), blood pressure, heart rate and dP/dt. Buthus occitanus venom (BO) was administered intravenously in the absence/presence of different pre-treatments. BO dose-dependently (150-300 microg/kg) increased blood pressure, dP/dt, total peripheral (TPR), renal (RVR) and muscular (HVR) vascular resistances, and decreased CO, RBF and HBF. Recovery occurred after 150 but not after 300 microg/kg. BO, 600 microg/kg, produced qualitatively similar effects but arrhythmias developed and mortality increased. Pre-treatment with phentolamine prevented the rises in TPR, RVR, HVR and blood pressure and the decreases in CO, RBF and HBF induced by BO, 300 microg/kg. Pre-treatment with propranolol prevented the rise in dP/dt and the occurrence of arrhythmias and limited the rise in RVR and the drop in RBF induced by BO, 300 microg/kg. Phentolamine, propranolol and their combination also prevented BO, 600 microg/kg-induced mortality. Other pre-treatments (bosentan, losartan, diltiazem, mepyramine) were almost ineffective vs. BO effects. Finally, BO, 300 microg/kg, induced a 30-40-fold increase in plasma epinephrine and norepinephrine levels, but no change in plasma endothelin-1 levels. Thus in anaesthetized rats, the pattern of the cardiac and systemic and regional haemodynamic effects of BO is typically that of and results from catecholamine outpouring-induced alpha- and beta-adrenoceptor stimulation.
Zeghal
K
K
Département de pharmacologie, Faculté de médecine de Sfax, Tunisia. jean-francois.giudicelli@kb.u-psud.fr
Sahnoun
Z
Z
Guinot
M
M
Richer
C
C
Giudicelli
J F
JF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012604:Scorpion Venoms / Q000008:administration & dosage / Q000633:toxicity*; D014655:Vascular Resistance / Q000187:drug effects
D002395:Catecholamines; D019332:Endothelin-1; D012604:Scorpion Venoms