Different Effects of Mg2+ on Endothelin-1− and 5-Hydroxytryptamine-Elicited Responses in Goat Cerebrovascular Bed

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 to ET-1 and 5-hydroxytryptamine (5-HT) during various Mg2+ treatments. We performed experiments in vitro by recording isometric tension in isolated 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 media containing 0 (Mg(2+)-free medium), 1 (control), and 10 mM Mg2+, but the influence of Mg2+ was different: Mg2+ deprivation increased sensitivity (EC50) and Mg2+ overload reduced contractility (Emax) of cerebral 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 relaxant response was lower at the ET-1 precontraction. Infusions of ET-1 (0.1 nmol/min) and 5-HT (10 micrograms/min) directly into the cerebroarterial 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 increased CBF and decreased cerebral vascular resistance, although this effect was less on ET-1-induced than on 5-HT-induced cerebral vasoconstriction.