Effects of CAS 754, a New Nitric Oxide Donor, on Regional Cerebral Blood Flow in Focal Cerebral Ischemia

Abstract

Nitric oxide (NO) plays an important role in regulating regional cerebral blood flow (rCBF). This study was performed to compare the effects of the NO donor, CAS 754, a sydnonimine derivative, and sodium nitroprusside (SNP) on rCBF in ischemic and nonischemic brain regions. Twenty-eight rats were anesthetized with 1.4% isoflurane and were mechanically ventilated. A middle cerebral artery (MCA) was occluded in each animal. In the CAS 754 group (n = 7), 40 min after MCA occlusion, 4-6 mg/kg of CAS 754 was administered intravenously (i.v.) to decrease the mean arterial blood pressure (MAP) to 55-60 mm Hg. In the SNP group (n = 7), an infusion of SNP was started to decrease the MAP to the same level as that of the CAS group. In the CAS-Ph group (n = 7), phenylephrine was infused after CAS754 had been administered in order to maintain the MAP at the control level (95-100 mm Hg). The remaining seven rats were used as a control group. rCBF was measured using 14C-iodoantipyrine in all four groups of animals 1 h after MCA occlusion (20 min after the start of drug administration). The average rCBF of the nonischemic brain regions (121 +/- 15 mL.min-1.100 g-1) was increased by 34% with CAS 754 (162 +/- 39 mL.min-1.100 g-1). However, SNP did not significantly change the average rCBF of the nonischemic brain regions (114 +/- 5 mL.min-1.100 g-1). Neither CAS 754 nor SNP significantly affected the rCBF of the ischemic cortex (control 51 +/- 7, CAS 61 +/- 13, SNP 53 +/- 18 mL.min-1.100 g-1). Phenylephrine infusion in the CAS 754-treated animals did not significantly affect the rCBF of the ischemic or nonischemic brain regions. In conclusion, our study demonstrated that CAS 754 was a more effective cerebral vasodilator than nitroprusside when administered systemically. In the ischemic cortex, neither CAS 754 nor nitroprusside improved rCBF Failure of CAS 754 to improve the rCBF of the ischemic cortex does not appear to be due to hypotension induced by CAS 754.