The Action of Ergotamine on the Intracranial Venous Pressure and on the Cerebral Venous Outflow of the Dog

Abstract

The effect of ergotamine and dihydroergotamine on the cerebral circulation was studied in the dog, anaesthetized with chloralose, by recording the intracranial venous pressure and the venous outflow from the superior cerebral vein. Under optimal experimental conditions, ergotamine (5 to 10 ,ug./kg.) and dihydroergotamine (100 ,ug./kg.) gave a marked and long-lasting cerebral vasoconstriction accompanied by a slight hypertension. The cerebral vasoconstriction provoked by ergotamine may be very small and was sometimes absent when the cerebral bloodflow was low. This vasoconstrictor effect is more pronounced the higher the initial intracranial venous pressure and hence the cerebral blood-flow. After the induction of a cerebral vasodilatation by 48/80 or strychnine, the vasoconstrictor action of ergotamine was more pronounced. The effect was not observed when CO, was employed to modify the intracranial venous pressure. Simultaneous registration of the cerebral, nasal cavity, and kidney vascular responses demonstrated the relative specificity of the action of ergotamine on the cerebral vessels. The small doses of ergotamine used may weaken or abolish the vasoconstrictor action of adrenaline on cerebral vessels. The modification of the responses of the cerebral circulation which such factors as anaesthesia, respiratory acidosis, and operative trauma can produce have been confirmed and emphasized. The results support the view that the vasoconstrictor action of ergotamine on the cerebral vessels might account for the therapeutic value of this drug in migraine.

The animal pharmacology of drugs used in the treatment of migraine

“…In experiments in dogs, evidence has been obtained for a selective vasoconstrictor effect of ergotamine in the carotid artery bed. Thus Carpi & Virno (1957) demonstrated a more marked vasoconstriction in the cerebral vessels than the vessels of the nose or kidney. Saxena & de VlaamSchluter (1974) extended these observations to include the whole of the carotid artery bed and the vasculature supplied by the femoral, superior mesenteric, renal, vertebral and coronary arteries.…”

“…Intravenous injections of ergotamine between 1 and 10 pg kg-l cause significant dose-related increases in arterial pressure in cats (Cerletti, Berde, & others, 1960) and dogs (Carpi & Virno, 1957;Cerletti & others, 1960;Wellens & Wauters, 1966a;Saxena & de Vlaam-Schluter, 1974). The effects are particularly long lasting and result from a widespread increase in peripheral resistance (Cerletti & others, 1960;Weidmann & Taeschler, 1966;Wellens & Wauters, 1966a, b;Saxena & de Vlaam-Schluter, 1974).…”

“…Even when systemic blood pressure falls after intravenous injection of dihydroergotamine in intact animals, there is evidence that some peripheral blood vessels (Rothlin, 1946(Rothlin, /1947Chu & Sturmer, 1973) including those of the cerebral vascular bed (Carpi & Virno, 1957) are constricted. When the vasomotor centres in the medulla or the efferent sympathetic pathways are inactivated (by for instance pithing or ganglion blockade), even small doses of dihydroergotamine cause peripheral vasoconstriction and through this an increase in blood pressure (Konzett & Rothlin, 1953).…”

Rapid Serial Angiography in the Investigation of the Pharmacology of Brain Circulation in the Dog

“…Previous work had demonstrated that this drug, administered intravenously in a dose of 10 jug./Kg., provokes a long-lasting fall in the intracranial venous pressure, which results from a vasoconstriction of the cerebral vessels. 9 This action is more evident in the dog in which a marked cerebral vasodilatation has been induced previously by strychnine. The experiments reported here indicate that the fall in the intracranial venous pressure was accompanied by a rise of the cerebral circulation time.…”

Peripheral Vasodilator Action of Eledoisin, Bradykinin, and Nitroglycerin in Anesthetized Dogs

“…Internal carotid artery blood flow measurements were made after ligation of the external carotid artery and all vessels near the bifurcation. Cerebral venous pressure was measured from a catheter in the external jugular vein; the significance of jugular pressure for the interpretation of cerebral vascular reactions has been discussed by Carpi and Virno 10 and by Bovet et al…”