MAGNESIUM-SULFATE REVERSES THE CAROTID VASOCONSTRICTION CAUSED BY ENDOTHELIN-I, ANGIOTENSIN-II AND NEUROPEPTIDE-Y, BUT NOT THAT CAUSED BY N(G)-NITRO-L-ARGININE METHYL-ESTER, IN CONSCIOUS RATS

1. Magnesium sulphate (MgSO4) has been used for many years in the prevention of eclamptic seizures, but its mechanism of action has never been elucidated. Recent studies suggest that cerebral vasospasm is an important feature of eclampsia and we have developed and tested the hypothesis that MgSO4 can reverse cerebral vasoconstriction. 2. Studies were performed in conscious, male Long Evans rats with pulsed Doppler probes sutured around both common carotid arteries after the external carotid artery had been ligated on the left, thus allowing simultaneous measurement of changes in common and internal carotid blood flow. Intravascular catheters were placed in the abdominal aorta for measurement of systemic blood pressure and in the right jugular vein for administration of drugs. Mean arterial blood pressure and mean Doppler shift signals were used to calculate percentage changes in common and internal carotid vascular conductance. 3. After a period of recovery the animals were infused with endothelin-1, angiotensin II, neuropeptide-Y or N(G)-nitro-L-arginine methyl ester alone or in combination, and MgSO4 in low or high dose was infused when the effects of the vasoconstrictors had become established. 4. MgSO4 itself, at the low dose, had no effect on carotid vascular conductance. Endothelin-1, angiotensin II and neuropeptide-Y all reduced common and internal carotid vascular conductance and this effect was significantly attenuated by low dose MgSO4. The carotid vasoconstrictor action of endothelin-1 was completely abolished by high dose MgSO4. Combinations of the peptides (endothelin-1/angiotensin II; endothelin-1/neuropeptide-Y; angiotensin II/neuropeptide-Y) also reduced common and internal carotid vascular conductance and these effects were substantially reversed, or completely abolished, by high dose MgSO4. The effect of N(G)-nitro-L-arginine methyl ester on common and internal carotid vascular conductance was significantly inhibited by human alpha-calcitonin gene-related peptide, but, in contrast, MgSO4 had no influence. 5. We have tested and confirmed our hypothesis that MgSO4 can reverse cerebral vasoconstriction. The failure of MgSO4 to influence the effects of N(G)-nitro-L-arginine methyl ester suggest that its vasodilator effect may involve the production of nitric oxide. These findings provide a basis for the action of MgSO4 in eclampsia, and suggest that it may be of value in other circumstances where cerebral vasoconstriction occurs.