VASOACTIVATORS - A NEW CONCEPT FOR NATURALLY SECRETED VASOCONSTRICTORSUBSTANCES

Many vasoconstrictor substances have been demonstrated as being vasodi lators through the mechanism of endothelium-derived relaxing factor (E DRF) release. The authors have hypothesized that all naturally secrete d vasoconstrictor substances may potentially be vasodilators as well i n order to maintain an adequate physiological vascular tone. To test t his hypothesis, they studied the effect of thromboxane A(2)-a naturall y secreted vasoconstrictor substance released from platelets, which ha s not been demonstrated as an EDRF stimulus, using its stable analog U 46619 in the porcine coronary artery (CA). The results have shown that U46619 is a stimulus for EDRF biosynthesis/release. This effect may b e blocked by the specific inhibitor of EDRF biosynthesis/release N-G-n itro-L-arginine (L-NNA). Therefore, this study supports the aforementi oned hypothesis. The authors suggest that naturally secreted vasoconst rictor substances may be more accurately termed ''vasoactivator'' subs tances. These vasoactivators, according to the balance between their c onstrictive or relaxing effects, may be classified as (1) Type I: vaso constriction-predominant type such as acetylcholine (ACh), and U46619 in porcine which mainly cause contraction in endothelium-intact arteri es; (2) Type II: balanced type such as norepinephrine (NE) and 5-hydro xytryptamine (5-HT) in porcine CA, which cause little contraction in e ndothelium-intact arteries but cause a great contraction when the endo thelium is denuded. Usually, the receptor subtypes located in the endo thelium and smooth muscle stimulated by any one of these vasoactivator substances are different. All these characteristics of vasoconstricto r substances may play an important role in maintaining an adequate vas cular tone.