Arabinda K. Sinha

Effects of Inhibition of Nitric Oxide Synthase on Blood-Brain Barrier Transport in Focal Cerebral Ischemia

This study was performed to determine whether nitric oxide (NO) alters the transport of small hydrophilic molecules across the blood-brain barrier in focal cerebral ischemia by administering an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and by measuring the blood-brain barrier transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid (14C-AIB) in the rats with middle cerebral artery occluded under isoflurane anesthesia. L-NAME increased the mean arterial blood pressure from 91 +/- 9 to 134 +/- 13 mm Hg. The Ki of the ischemic cortex (ICO) was 26% higher than that of the contralateral cortex (CCO) in the control animals without the L-NAME treatment. However, in the L-NAME-treated animals, Ki was 33% lower in the ICO than in the CCO. The Ki of ICO in the L-NAME group was significantly lower (-54%) than that of the control group. L-NAME did not affect Ki significantly in the nonischemic brain regions. Our data demonstrate that focal ischemia increased Ki of 14C-AIB, but L-NAME significantly decreased the Ki in the focal ischemic area of the brain without causing significant changes in the nonischemic tissue. Our results suggest that NO may participate in increasing transport of small hydrophilic molecules across the blood-brain barrier in focal ischemia.

Effects of isoflurane on transport across the blood-brain barrier

The blood-brain barrier (BBB) plays an important role in regulating and restricting transfer of molecules into the interstitial space of the brain. Anesthetic agents may affect the permeability of the BBB. In this investigation, the effect of isoflurane on the transport of small hydrophilic molecules across the BBB was studied in rats by measuring the blood-brain transfer coefficient (Ki) and the regional cerebral blood flow (rCBF) and by calculating the capillary permeability-surface area (PS) product. In the control group, after a femoral artery and vein were catheterized under isoflurane anesthesia, rats were allowed to remain awake for 2 h before measuring Ki (n = 6) or rCBF (n = 11). In the two experimental groups, rats were anesthetized with 1% and 2% isoflurane respectively, and their lungs were mechanically ventilated through a tracheal tube. Ki was measured (1% n = 6, 2% n = 7) using 14C-alpha-aminoisobutyric acid, and rCBF was measured (2% n = 7) using 14C-iodoantipyrine. Two percent isoflurane did not affect rCBF in 9 of 13 brain regions. Blood flow was less in the lateral and posterior cortex and greater in the medulla and pons when compared with the control group. Ki was less in 11 of 13 brain regions in both the 1% and 2% isoflurane groups than in the control group. There was no significant difference between 1 and 2% isoflurane in any brain region.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of nitric oxide synthase inhibition on regional cerebral blood flow and vascular resistance in conscious and isoflurane-anesthetized rats

Nitric oxide is an important regulator of the regional cerebral vascular tone. We compared the magnitude of nitric oxide-related changes in the vascular tone by studying the regional cerebral blood flow (rCBF) and vascular resistance in conscious and isoflurane-anesthetized rats by using a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). In the conscious group (n = 12), after cannulation of a femoral artery and two veins under isoflurane anesthesia, rats were allowed to remain awake for 90 min. In the anesthetized group (n = 18), rats were anesthetized with 2% isoflurane and mechanically ventilated. Six rats in each group were treated with L-NAME (2 mg.kg-1 x min-1 for 30 min) or saline. For the remaining rats in the isoflurane-anesthetized group (n = 6), arterial blood pressure was increased by phenylephrine infusion to the same level as that in the L-NAME-treated, isoflurane-anesthetized rats. Regional vascular resistance was determined by the ratio of mean arterial blood pressure and rCBF which was measured by [14C]iodoantipyrine. L-NAME significantly increased mean arterial blood pressure in both the conscious (123 to 158 mm Hg) and anesthetized (82 to 144 mm Hg) rats. Regional vascular resistance increased significantly in all 12 brain regions studied with the average value increasing from 1.19 +/- 0.33 mm Hg.mL-1 x min x 100 g to 2.22 +/- 0.48 (P < 0.0001) in the conscious and from 0.78 +/- 0.27 to 1.61 +/- 0.48 (P < 0.0001) in the isoflurane-anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of MK-801 on cerebral regional oxygen consumption in focal cerebral ischemia in rats.

This investigation tested in rats whether MK-801, an N-methyl-D-aspartate receptor antagonist, would improve the balance of oxygen supply and consumption in the focal ischemic area of the brain induced by occlusion of the middle cerebral artery. Fifteen minutes after middle cerebral artery occlusion, 5 mg/kg MK-801 was administered intravenously to the MK-801 group (n = 12), and normal saline was given to the control group (n = 12). One hour after the occlusion in each group, regional cerebral blood flow was determined in six rats using [14C]iodoantipyrine, and regional arterial and venous oxygen saturations were determined using a microspectrophotometric technique in the other six rats. In both groups of animals, the cerebral blood flow of the ischemic cortex was significantly lower than that of the contralateral cortex (36 +/- 16 [SD] and 67 +/- 14 ml/min/100 g for the control group; 33 +/- 10 and 58 +/- 11 ml/min/100 g for the MK-801 group, respectively). Oxygen extraction was significantly higher in the ischemic cortex (8.8 +/- 2.1 ml O2/100 ml blood) than in the contralateral cortex (5.6 +/- 0.3) for the control group. However, for the MK-801 group, there was no significant difference between the ischemic cortex (6.1 +/- 1.0) and the contralateral cortex (5.7 +/- 1.1). Oxygen extraction in the ischemic cortex of the MK-801 group was significantly lower than that of the control group. Calculated ischemic regional oxygen consumption was similar to the nonischemic values in the control group, whereas the ischemic value was reduced to 61% of the value of the contralateral cortex in the MK-801 group.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide synthase inhibition alters cerebral blood flow and oxygen balance in focal cerebral ischemia in rats.

Background and Purpose This study investigated whether the nitric oxide synthase inhibitor N

Effect of hypoxic-hypocapnia on cerebral regional oxygen consumption and supply

-nitro-L-arginine-methyl ester (L-NAME) would alter blood flow and oxygen balance in the ischemic cerebrocortex of isoflurane-anesthetized Long-Evans rats. Methods Fifteen minutes after middle cerebral artery occlusion, L-NAME (1.5 mg/min per kilogram) was infused intravenously to the L-NAME group (n=14), and normal saline was given to the control group (n=14) for 45 minutes. In each group, regional cerebral blood flow was determined with [14C]iodoantipyrine, and arterial and venous oxygen saturations were determined by microspectrophotometry. Results In both groups regional cerebral blood flow of the ischemic cortex was significantly lower than that of the contralateral cortex ([mean

Effects of Pentobarbital and Isoflurane on Regional Cerebral Oxygen Extraction and Consumption with Middle Cerebral Artery Occlusion in Rats

SD] 55