The aim of this study was to determine the effects of endogenous nitric oxide (NO) on cerebral blood flow (CBF) and cerebrovascular resistance (CVR) under conditions of normoxia and hypoxia. Experiments were performed on anesthetized, mechanically ventilated Wistar rats. CBF was measured using the intracarotid¹³³Xe injection technique. NO formation was inhibited by N^G-monomethyl-l-arginine (l-NMMA). Administration of l-NMMA (100 mg kg⁻¹i.v.) during normoxia resulted in an increase in mean arterial blood pressure from 113 ± 4 to 145 ± 4 mm Hg ( p < 0.001), a decrease in CBF of 21% (from 91 ± 4 to 75 ± 5 ml 100 g⁻¹min⁻¹, p < 0.001), and an increase in CVR of 53% (from 1.3 ± 0.1 to 2.0 ± 0.2 mm Hg ml⁻¹100 g min, p < 0.001). These effects were reversed by i.v. administration of 300 mg kg⁻¹of l-arginine but not d-arginine. Moreover, the administration of l-NMMA abolished the enhancement of CBF and the diminution in CVR observed during intracarotid infusion of acetylcholine (ACh). The increase in CBF and decrease in CVR during hypoxia in the group of rats that received l-NMMA were similar to that in the control group, although CBF and CVR levels attained during hypoxia in both groups were different. The results show that NO is involved in the maintenance of basal CBF and CVR, and is responsible for the ACh-elicited increase in CBF and the decrease in CVR in rats. They also suggest that NO modulates hypoxic changes of CBF and CVR, but is probably not the main factor responsible for the increase in CBF during hypoxia.

Experimental evidence obtained in various animal models of brain injury indicates that vasopressin promotes the formation of cerebral edema. However, the molecular and cellular mechanisms underlying this vasopressin action are not fully understood. In the present study, we analyzed the temporal changes in expression of vasopressin V_1a receptors after traumatic brain injury (TBI) in rats. In the intact brain, the V_1a receptor was expressed in neurons located in all layers of the frontoparietal cortex. The V_1a receptor-immunoreactive product was predominantly localized to neuronal nuclei and had both a diffused and punctate staining pattern. The V_1a receptors were also expressed in astrocytes, especially in layer 1 of the frontoparietal cortex. In these cells, two distinctive patterns of immunopositive staining for V_1a receptors were observed: a diffused cytosolic staining of cell bodies and processes and a clearly punctate staining pattern that was predominantly localized to the astrocytic cell bodies. The real-time reverse-transcriptase polymerase chain reaction analysis of changes in mRNA for the V_1a receptor demonstrated that after TBI, there is an early (4 h post-TBI) increase in the number of transcripts in the ipsilateral frontoparietal cortex, when compared to the contralateral hemisphere or the sham-injured rats. This increase in the message was followed by the up-regulation of expression of the V_1a receptors at the protein level. This was most evident in cortical astrocytes in the areas surrounding the lesion. The number of the V_1a receptor-immunopositive astrocytes in the traumatized parenchyma gradually increased, starting at 8 h and peaking at 4–6 days after TBI. Furthermore, a redistribution of V_1a receptors from the astrocytic cell bodies to the astrocytic processes was observed. In addition to astrocytes, an increased expression of V_1a receptors was found in the endothelium of both blood microvessels and the large-diameter blood vessels in the frontoparietal cortex ipsilateral to injury. This increase in the V_1a receptor expression was apparent between 2 and 4 days after TBI. As early as 1–2 h following the impact, there was also a striking increase in the number of the V_1a receptor-immunopositive beaded axonal processes, with greatly enlarged varicosities, that were localized to various areas of the injured parenchyma. It is suggested that the increased expression of V_1a receptors plays an important role in the vasopressin-mediated formation of edema in the injured brain.