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 particular interest is the increased responsiveness to vasoconstrictors, e.g., 5-hydroxy tryptamine and noradrenaline, and the decreased reactivity towards vasodilators, e.g., acetylcholine. This, together with the 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 (MPPG) has been shown to effectively reduce serum lipids in animals and in man, and to retard the progression of atherosclerotic lesions in experimental animals. It was therefore considered of interest to investigate the reactivity of both the aorta and the renal artery to different vasoactive substances in hypercholesterolemic rabbits under the influence of MPPG as well as the effect of such substances on the blood pressure of the anesthetized animals. The rabbits were fed a high cholesterol diet for 2 months, followed by MPPG for 1 month, while keeping the rabbits on the same diet. One batch of animals was used for blood pressure recording and testing drug effects, and another was used for testing the responsiveness of their aortae and renal arteries to the different mediators. In hypercholesterolemic rabbits, treatment with MPPG tended to normalize the increased responsiveness of the blood pressure to the vasoconstrictors: noradrenaline and angiotensin and the diminished sensitivity to histamine and acetylcholine. For the isolated arteries, however, MPPG did not significantly affect the responses to noradrenaline nor potassium chloride, but tended to normalize responses to clonidine and acetylcholine. It could be concluded from the present findings that the high cholesterol diet induces changes in vascular reactivity which are possibly related to endothelial and/or receptor sensitivity changes. Treatment with MPPG helps to reverse these changes and to restore normal vascular reactivity, a fact that could have important clinical implications in the management of cardiovascular diseases.
Khayyal
M T
MT
Department of Pharmacology, Faculty of Pharmacy, Cairo University, Egypt.
Khayyal
M A
MA
Sharaf
H M
HM
el-Sherbeeny
M
M
Okpanyi
S N
SN
Schneider
W
W
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D003000:Clonidine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005973:Glutamine / Q000627:therapeutic use*; D006632:Histamine / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000209:etiology; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000627:therapeutic use*; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects*
D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D014662:Vasoconstrictor Agents; D005973:Glutamine; D000804:Angiotensin II; D011732:Pyridoxal Phosphate; C047672:magnesium-pyridoxal-5'-phosphate glutamate; D006632:Histamine; D003000:Clonidine; D000109:Acetylcholine; D009638:Norepinephrine