Vascular Effects of PHYSALIA PHYSALIS Venom

Abstract

The purpose of this study was to identify the effects of Physalia physalis (Portuguese Man-of-War) venom on vascular smooth muscle and elucidate its mode of action. We utilized the in vivo approach by functionally isolating the skeletal muscle vasculature of the dog\u27s hind leg, and the in vitro approach by studying rabbit arterial ring segments. Twelve male mongrel dogs were anesthetized with 35 mg/kg sodium pentobarbital. Arterial pressure was measured from the aortic arch and the cranial femoral artery, a cephalad branch of the femoral artery. The skeletal muscle venous blood flow of the hind leg was functionally isolated. Femoral vein blood flow and pressure were monitored from ports in the extracorporeal flow sensor. Four of the twelve dogs were also subjected to lumbar sympathetic chain stimulation. Lingual, renal, femoral and central ear arterial ring segments were excised from 19 male California rabbits, weighing less than 2.7 kg. These vascular segments were each mounted on an isometric tension measuring device and placed in a 15 ml bath filled with Krebs-Henseleit solution aerated with 95% O2 and 5% CC^. Each ring was set at its optimum basal tension by applying passive stretch and inducing constriction with norepinephrine. The venom was added to the bath in logarithmically spaced doses, ranging from 0.021 yg/ml to 4.28 yg/ml. It was found that Physalia venom increased skeletal muscle blood flow when it was injected into the cranial femoral artery. The effect of the venom was diminished by cimetidine and tripelennamine (histamine receptor blockers), and was blocked by sodium meclofenamate (prostaglandin synthesis inhibitor). The venom transiently reversed sympathetic vasoconstriction, and no change of this effect was noted with infusion of cocaine. Venous blood samples taken after infusion of the venom revealed higher histamine levels than the control samples. The venom produced relaxation of the arterial ring segments in a sigmoid dose-dependent manner. The femoral artery displayed the greatest sensitivity to the venom, but the highest efficacy was demonstrated on the lingual artery. This effect was almost completely blocked by pretreatment with sodium meclofenamate. Venom induced relaxation was slightly enhanced by pretreatment with propranolol, but not significantly from control. Quinacrine (phospholipase A2inhibitor) and atropine had no effect on venom-induced relaxation. These observations suggest that Portuguese Man-of-War venom is a vasodilator, and that the primary mode of action is through stimulation of the synthesis of vasodilatory prostaglandins from substrates that are independent of phospholipase A2 activity