Effects of nimodipine on cerebral blood flow in conscious rat.
The purpose of this study was to determine the effects of the calcium channel blocker nimodipine (NM) on cerebral blood flow in the rat under conscious and anesthesized conditions and to compare these to effects of the drug in other circulations. Regional blood flows were measured using the radioactive microsphere technique. Hemodynamic parameters were assessed at the time of blood flow determinations in conscious rats and in pentobarbital-anesthetized rats. NM was administered i.v. using a cumulative dosing regimen in conscious (6, 24 and 60 micrograms/kg) and anesthetized (6 and 60 micrograms/kg) rats. In conscious rats, NM dose-dependently increased coronary blood flow whereas significantly lowering pressure-rate product and slightly but significantly reduced mean arterial pressure and systemic vascular resistance. In conscious rats, NM had no significant effect on cerebral blood flow or cerebral vascular resistance. In anesthetized rats, cerebral and systemic vascular resistances were higher compared to conscious animals. In anesthetized animals, NM reduced mean arterial pressure and systemic resistance to a greater extent than in conscious rats and significantly increased cerebral blood flow. Base-line coronary resistance was similar in conscious and anesthetized rats and the coronary dilator effects of NM were also similar under the two conditions. These findings suggest that NM is not a selective cerebral vasodilator in rats and that the cerebral dilator effects of this drug are not apparent in conscious rats. Only under the high cerebral resistance condition induced by pentobarbital anesthesia was NM found to be a cerebral vasodilator in the rat.
D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D008297:Male; D009539:Nicotinic Acids / Q000494:pharmacology*; D009553:Nimodipine; D010424:Pentobarbital / Q000494:pharmacology; D005082:Physical Exertion; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D009539:Nicotinic Acids; D014665:Vasodilator Agents; D009553:Nimodipine; D010424:Pentobarbital