Effect of Centrally Administered Encephalinamides on Regional Cerebral Blood Flow in the Dog

Abstract

(D-ala²)-met⁵-encephalinamide (AM encephalinamide) and (D-ala²)-leu⁵-encephalinamide (AL encephalinamide) were administered into the cisterna magna in anesthetized dogs to determine whether these opiates effected the neurohypophyseal circulation differently than the circulation of other brain areas. At the beginning of the experimental protocol, animals were given either mock cerebral spinal fluid (CSF) or 5 or 25 mg of AM encephalinamide or 5 mg of AL encephalinamide in equal volumes of mock CSF into the cisterna magna. By 60 min after intracisternal injection, radiolabeled AM encephalinamide distributed throughout the brain with the highest concentration being in the area of the brainstem. Sixty minutes after intracisternal injection, heart rate was decreased 29.0 ± 5.1%, 41.3 ± 4.4%, and 36.0 ± 3.6%, and MABP was decreased 25.2 ± 8.0%, 26.4 ± 2.4%, and 32.3 ± 2.6% in animals treated with AL encephalinamide (5 mg), AM encephalinamide (5 mg), and AM encephalinamide (25 mg), respectively. Neither AL encephalinamide or AM encephalinamide altered CBF or CMRO₂ when compared with animals treated with mock CSF, whereas both AL encephalinamide and AM encephalinamide reduced neurohypophyseal blood flow by 30 min (43 ± 11%, AL encephalinamide; 35 ± 7%, AM encephalinamide, 5 mg; 46 ± 8%, AM encephalinamide, 25 mg); the reduction was sustained throughout the 60-min protocol (34 ± 10%, AL encephalinamide; 37 ± 3%, AM encephalinamide, 5 mg; 38 ± 4% AM encephalinamide, 25 mg). Plasma arginine vasopressin was transiently elevated 15 (326 ± 75%, AL encephalinamide; 323 ± 109%, AM encephalinamide, 25 mg) and 30 min (271 ± 68%, AL encephalinamide; 368 ± 136%, AM encephalinamide, 25 mg) in animals treated with AL encephalinamide or AM encephalinamide (25 mg). Intravenous naloxone administered at the end of the 60-min encephalinamide protocol was associated with a rise toward control values in heart rate and MABP in the AL encephalinamide group and in heart rate, MABP, and neurohypophyseal blood flow in both the AM encephalinamide 5 mg and 25 mg groups. These data suggest that encephalinamides may play a role in the regulation of neurohypophyseal blood flow through their actions on opiate receptors.