Effects of VX and soman on vascular contractility in isolated rat and guinea pig aorta

Abstract

The mechanism of organophosphorous nerve agents is inhibition of cholinesterase. The effect of in vivo nerve agent exposure on isolated vascular contractility is unknown. Since disruption of the cholinergic signaling cascade by nerve agent exposure could have detrimental effects on vascular function, we hypothesized that exposure to nerve agents would alter isometric force development. Integrity of vascular smooth muscle voltage and receptor-mediated contractile responses was evaluated in adult male rats and guinea pigs. Aortic rings were isolated from the animals one hour after a sublethal exposure (0.4, 0.6, or 0.8 LD50) to VX or soman (GD). Response to potassium chloride (KCl) and phenylephrine (PE) was measured in an organ bath apparatus. Force development to KCl or PE was depressed in aorta from VX-exposed rats, but increased after GD exposure. Guinea pig aorta exhibited a slight depression in KCl and PE induced at the highest VX dose. Conversely, the lower dose of GD caused an increase in guinea pig aortic force development, while the higher doses remained at, or near, control levels. These data suggest a nerve agent-induced change in vascular force regulation that is species-specific and distinct between VX and GD. The results will provide an indication of the functional consequences following in vivo exposure to nerve agents and assist in developing medical countermeasures against chemical warfare agents.