DIFFERENT EFFECTS OF MG2-1-HYDROXYTRYPTAMINE AND 5-HYDROXYTRYPTAMINE ELICITED RESPONSES IN GOAT CEREBROVASCULAR BED( ON ENDOTHELIN)

Mg2+ influences the response of cerebral arteries to several agonists, but until now its effects on endothelin-1 (ET-1) had not been studied . We recorded and compared the responses of goat cerebrovascular bed t o ET-1 and 5-hydroxytryptamine (5-HT) during various Mg2+ treatments. We performed experiments in vitro by recording isometric tension in is olated goat middle cerebral arteries and in vivo by recording cerebral blood flow (CBF) and other physiologic parameters in conscious goats. Cumulative addition of ET-1 (10(-11)-3 x 10(-8)M) and 5-HT(10(-9)-10( -5)M) contracted cerebral arteries concentration dependently in bath m edia containing 0 (Mg2+- free medium), 1 (control), and 10 mM Mg2+, bu t the influence of Mg2+ was different: Mg2+ deprivation increased sens itivity (EC(50)) and Mg2+ overload reduced contractility (E(max)) of c erebral arteries to 5-HT, whereas the ET-1 response did not change in these conditions. Cumulative addition of Mg2+ (10(-4)-3 x 10(-2)M) at the active tone induced by ET-1 (10(-9)M) and 5-HT (10(-5)M) elicited concentration-dependent relaxations of cerebral arteries, but the rela xant response was lower at the ET-1 precontraction. Infusions of ET-1 (0.1 nmol/min) and 5-HT (10 mu g/min) directly into the cerebroarteria l supply of the unanesthetized goats elicited a sustained decrease in CBF and an increase in cerebral vascular resistance. Magnesium sulfate , administered as increasing doses (10-300 mg) in the same way increas ed CBF and decreased cerebral vascular resistance, although this effec t was less on ET-1-induced than on 5-HT-induced cerebral vaso-constric tion. When infused intravenously (i.v.; 3 g/15 min), magnesium sulfate had no effect on the ET-1-induced cerebral vasoconstriction, but incr eased 5-HT-reduced CBF. ET-1 is a relatively Mg2+-resistant contractil e stimulus in the cerebrovascular bed. This should be taken into accou nt in consideration of the therapeutic potential of Mg2+ in cerebrovas cular disorders in which ET-1 might be involved.