Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat.
The vasomotor effects of ergotamine and dihydroergotamine (DHE) on the middle cerebral artery (MCA) of rats were studied using the pressurised arteriography method and in vitro myographs. MCAs from Sprague-Dawley rats were mounted on two glass micropipettes using the arteriograph, pressurised to 85 mmHg and luminally perfused. All vessels used attained spontaneous contractile tone (34.9+/-1.8% of resting tone) and responded to luminal adenosine triphosphate (ATP) with dilatation (24.1+/-4.0%), which showed functioning endothelium. Luminally added ergotamine or DHE induced maximal contractions of 16.8+8% and 22.4+/-0.9%, respectively, compared to the resting diameter, with a pEC(50) of 8.7+/-0.1 for ergotamine and 9.0+/-0.1 for DHE. Abluminal application of ergotamine and DHE also caused concentration-dependent contractions of the perfused MCA by 21.4+/-2.1% and 23.1+/-7.0%, respectively, with pEC(50) values of 7.6+/-0.2 for ergotamine and 8.4+/-0.5 for DHE. The responses were blocked by the 5-HT(2A) receptor antagonist ketanserin (concentration 10(-12) to 10(-5) M) and partially with the 5-HT(1B) receptor antagonist BRL-11557PM-B. The 5-HT(1D) receptor antagonist SB-224289-A had no significant effect. Using a myograph technique, isolated ring segments of the MCA with intact endothelium were mounted on two metal wires. Neither agonist caused relaxation of resting vessels, however, they both responded by weak contractile responses (26+/-3% of submaximal contractile capacity relative to 60 mM potassium). The contractions were typically slow in on and off set (about 30-60 min). The long duration of ergots should be investigated further in an attempt to design drugs with less recurrence.
Tfelt-Hansen
Peer
P
Department of Neurology, Copenhagen University Hospital, Glostrup, Denmark.
Nilsson
Elisabeth
E
Edvinsson
Lars
L
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000818:Animals; D025441:Dihydroergocornine / Q000008:administration & dosage*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004878:Ergotamine / Q000008:administration & dosage*; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D018491:Dopamine Agonists; D012702:Serotonin Antagonists; D025441:Dihydroergocornine; D004878:Ergotamine