EFFECT OF MAGNESIUM PYRIDOXAL 5-PHOSPHATE GLUTAMATE ON VASCULAR REACTIVITY IN EXPERIMENTAL HYPERCHOLESTEROLEMIA

Hypercholesterolemia is known to affect the responsiveness of various blood vessels to endogenous and to exogenous vasoactive agents. Of par ticular interest is the increased responsiveness to vasoconstrictors, e.g., 5-hydroxy tryptamine and noradrenaline, and the decreased reacti vity towards vasodilators, e.g., acetylcholine. This, together with th e development of arteriosclerosis, could play an important role in the progression of many vascular complications, such as hypertension and coronary heart disease. Magnesium pyridoxal 5-phosphate glutamate (MPP G) has been shown to effectively reduce serum lipids in animals and in man, and to retard the progression of atherosclerotic lesions in expe rimental animals. It was therefore considered of interest to investiga te the reactivity of both the aorta and the renal artery to different vasoactive substances in hypercholesterolemic rabbits under the influe nce or MPPG as well as the effect of such substances on the blood pres sure of the anaesthetized animals. The rabbits were fed a high cholest erol diet for 2 months, followed by MPPG for I month, while keeping th e rabbits on the same diet One batch of animals was used for blood pre ssure recording and testing drug effects, and another was used for tes ting the responsiveness of their aortae and renal arteries to the diff erent mediators. In hypercholesterolemic rabbits, treatment with MPPG fended to normalize the increased responsiveness of the blood pressure to the vasoconstrictors: noradrenaline and angiotensin and the dimini shed sensitivity to histamine and acetylcholine. For the isolated arte ries, however, MPPG did not significantly affect the responses to nora drenaline nor potassium chloride, but tended to normalize responses to clonidine and acetylcholine. If could be concluded from the present f indings that the high cholesterol diet induces changes in vascular rea ctivity which are possibly related to endothelial and/or receptor sens itivity changes. Treatment with MPPG helps to reverse these changes an d to restore normal vascular reactivity, a fact that could have import ant clinical implications in the management of cardiovascular diseases .