Effects of topical and intravenous JM-1232(-) infusion on cerebrovascular reactivity in rats

Abstract

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.

Keywords: Cerebrovascular reactivity; Cranial window; JM-1232(−).