Molecular Mechanisms of Physalia Physalis Venom Modulation of Cardiac and Vascular Functions

<p>Portuguese man-of-war <em>(Physalia physalis)</em>venom has profound effects on the cardiovascular system of man and animals. The venom produces vascular relaxation in norepinephrine precontracted, intact rabbit femoral arterial rings by stimulating vasodilatory prostaglandin synthesis in the endothelium. This action does not depend on endotheliumderived relaxing factor (EDRF). <em>P. physalis </em>venom produces a vascular constriction on KC1 depolarized, intact rings. This is completely inhibited by dibenzyline and yohimbine. Increased membrane permeability to calcium may be involved in direct vascular smooth muscle stimulation. The venom has a positive inotropic effect on rat atrial preparations, which is intensified by increased extracellular calcium concentration. <em>P. physalis </em>venom markedly increases calcium influx of cultured embryonic chick heart cells in a dose dependent manner by activating L type calcium channels. The increased calcium influx is consistent with the positive inotropic action on the cultured heart cells observed under the microscope. This effect is completely inhibited by diltiazem and verapamil. Sodium influx of cultured embryonic chick heart cells is moderately increased (about one sixth of increased calcium influx) under the influence of <em>P. physalis </em>venom. Flecainide (a sodium channel blocker) and verapamil do not inhibit the increased sodium influx. The venom may accelerate sodium/calcium exchange directly and/or indirectly by increased calcium influx, the major mechanism for the embryonic chick heart to eliminate excessive cytoplasmic free calcium. Rubidium (an analog of potassium) influx is not affected by <em>P. physalis </em>venom at lower dose levels. A high concentration of the venom, nevertheless, decreases rubidium influx, implicating an inhibition of the Na+, K+-pump. Greatly increased contraction of the cultured heart cells associated with a large calcium influx may result in energy depletion, hence, inhibition of the Na+, K+-pump. The increased calcium influx of the cultured heart cells appears to be highly correlated with an increased efflux of rubidium. Stimulation of calcium-dependent potassium channels is an indirect effect of the venom. Activation of ATP-sensitive potassium channels may also contribute to the increased rubidium efflux when ATP depletion occurs under the condition of greatly increased contraction in the presence of a high venom concentration. <em>P. physalis</em> venom does not affect 2-deoxy-D-glucose uptake by cultured embryonic chick heart cells. However, at extremely high doses the uptake of the glucose is reduced. Glucose transport and metabolism may be disturbed by the excessive cytoplasmic calcium caused by <em>P. physalis</em> venom.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Pharmacology

Year

1990

Author dc:creator

• Luo, Eva

Contributors dc:contributor

• Ramon R. Gonzalez
• David A. Hessinger
• Ian M. Fraser
• Marvin A. Peters
• Allen Strother
• Robert A. Chilson

• Biology
• Pharmacology
• Physiology
• Portuguese Man-of-war; Venoms; Marine Toxins; Cardiovascular System -- pathology

Statement dc:rights

• This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/907

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-2032