Diminished effect of inhibition of nitric oxide synthase on regional cerebral vascular resistance in conscious and in isoflurane anesthetized rats during hemorrhage

Effects of a nitric oxide (NO) synthase inhibitor on regional cerebral vascular resistance (rCVR) and regional cerebral blood flow (rCBF) were studied during a severe hemorrhage in conscious and in isoflurane anesthetized groups of rats. Half of each group was infused with N^G-nitro-l-arginine-methyl ester (l-NAME), a NO synthase inhibitor, at a rate of 2 mg·kg^-1·min^-1 for 30 min. Half of the lNAME infused and half of the normal saline infused rats were bled to reduce the mean arterial blood pressure (MAP) to 44-49 mmHg. rCBF was measured using [¹⁴C]iodoantipyrine. rCVR was calculated as the ratio of MAP to rCBF. In the conscious non-hemorrhagic rats, l-NAME markedly increased rCVR in all the brain regions that we studied. In the conscious rats without l-NAME treatment, hemorrhage decreased rCVR in most of the brain regions. With l-NAME treatment in this group, hemorrhage increased rCVR only in the rostral part of the brain. Isoflurane decreased rCVR in most of the brain regions except the cortical area. l-NAME markedly increased rCVR in all the brain regions that we studied in the isoflurane anesthetized rats. In the isoflurane anesthetized rats, hemorrhage did not reduce rCVR in any of the brain regions. In the isoflurane anesthetized hemorrhagic rats, l-NAME did not significantly affect rCVR in any of the brain regions that we studied. We found that l-NAME increased rCVR to a greater extent in the non-hemorrhagic rats than in the hemorrhagic rats in both the conscious and in the isoflurane anesthetized rats. The effect of l-NAME appeared to be similar both under conscious and under isoflurane anesthetized conditions.