VASOACTIVATORS - A NEW CONCEPT FOR NATURALLY SECRETED VASOCONSTRICTOR SUBSTANCES

Many vasoconstrictor substances have been demonstrated as being vasodilators through the mechanism of endothelium-derived relaxing factor (EDRF) release. The authors have hypothesized that all naturally secreted vasoconstrictor substances may potentially be vasodilators as well in order to maintain an adequate physiological vascular tone. To test this hypothesis, they studied the effect of thromboxane A(2)-a naturally secreted vasoconstrictor substance released from platelets, which has not been demonstrated as an EDRF stimulus, using its stable analog U46619 in the porcine coronary artery (CA). The results have shown that U46619 is a stimulus for EDRF biosynthesis/release. This effect may be blocked by the specific inhibitor of EDRF biosynthesis/release N-G-nitro-L-arginine (L-NNA). Therefore, this study supports the aforementioned hypothesis. The authors suggest that naturally secreted vasoconstrictor substances may be more accurately termed ''vasoactivator'' substances. These vasoactivators, according to the balance between their constrictive or relaxing effects, may be classified as (1) Type I: vasoconstriction-predominant type such as acetylcholine (ACh), and U46619 in porcine which mainly cause contraction in endothelium-intact arteries; (2) Type II: balanced type such as norepinephrine (NE) and 5-hydroxytryptamine (5-HT) in porcine CA, which cause little contraction in endothelium-intact arteries but cause a great contraction when the endothelium is denuded. Usually, the receptor subtypes located in the endothelium and smooth muscle stimulated by any one of these vasoactivator substances are different. All these characteristics of vasoconstrictor substances may play an important role in maintaining an adequate vascular tone.