Effects of topical and intravenous JM-1232(-) infusion on cerebrovascular reactivity in rats.
A novel short-acting benzodiazepine receptor agonist, JM-1232(-), has been shown to have a sedative/hypnotic effect and wide safety margin. However, its effect on cerebral vessels is not well known. Therefore, we investigated the cerebrovascular reactivity to topical and intravenous JM-1232(-) and during hypotension or hypercapnia with intravenous administration of JM-1232(-). We used a closed cranial window preparation to measure the changes of cerebral pial arteriolar diameters in isoflurane-anesthetized Sprague-Dawley rats. We first measured the direct effect of topical JM-1232(-). We then determined the effect of intravenous JM-1232(-) and then we measured the response to hypercapnia before and after JM-1232(-) infusion. Finally, we measured the reaction to stepwise induction of hypotension before and after JM-1232(-) infusion. Topical infusion of JM-1232(-) dilated pial arterioles. Intravenous infusion of JM-1232(-) changed pial arterioles by 4.5 ± 2.7 %, 5.0 ± 3.9 %, and -2.8 ± 2.6 % (at 0.1, 0.3, and 1.0 mg/kg/min, respectively). Hypercapnia dilated pial arterioles before and after JM-1232(-) infusion. The diameters of pial arterioles did not change during hypotension before or after intravenous JM-1232(-) infusion. These results indicate that topical JM-1232(-) has a dilative effect on pial arterioles and that intravenous administration of JM-1232(-) may not affect cerebrovascular reactivity to hypotension or hypercapnia.
Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu-City, Gifu, 501-1194, Japan.
Kenji
K
Iwata
Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu-City, Gifu, 501-1194, Japan. iida@gifu-u.ac.jp.
Hiroki
H
Iida
Division of Internal Medicine and Cardiology, Gifu Prefectural General Medical Center, Gifu, Japan.
Mami
M
Iida
Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu-City, Gifu, 501-1194, Japan.
Naokazu
N
Fukuoka
Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu-City, Gifu, 501-1194, Japan.
Kazuhiro
K
Kito
Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu-City, Gifu, 501-1194, Japan.
Kumiko
K
Tanabe
D000287:Administration, Topical; D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D006935:Hypercapnia / Q000378:metabolism; D007262:Infusions, Intravenous; D007530:Isoflurane / Q000008:administration & dosage; D054833:Isoindoles / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D010841:Pia Mater / Q000098:blood supply*; D010879:Piperazines / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
C534223:3-(2-(4-methyl-1-piperazinyl)-2-oxoethyl)-2-phenyl-3,5,6,7-tetrahydrocyclopenta(f)isoindol-1(2H)-one; D054833:Isoindoles; D010879:Piperazines; D007530:Isoflurane
Cerebrovascular reactivity; Cranial window; JM-1232(−)