its expression in these cells, including those found in the cerebral vasculature. Further, other immunohistochemical studies have also detected NOS immunoreactivity in cerebral microvessels, while Pluta and colleagues have found a marked loss of nNOS immunoreactivity in vasospastic cerebral arteries [8]. Second, several pharmacological studies using inhibitors of NOS, such as L-NMMA, have reported endothelium-dependent contractions to these agents in resting cerebral blood vessels - effects reversed by the NOS substrate L-argi-nine [9,10]. Endothelium-independent contractions to L-NMMA have also been observed in cerebral blood vessels, indicating that the inhibition of non-endothelial sources of NOS, i.e. constitutive in perivascular nerve fibers or induced in vascular smooth muscle, may also be involved. Third, physiological studies involving transmural electrical nerve stimulation of isolated cerebral arteries have also shown that vasorelaxation produced by this means is abolished by L-NMMA, hemoglobin and extracellular calcium depletion - findings consistent with the active presence of NOS here [11]. Last, recent advances in molecular biology have facilitated a greater understanding of the cere-brovascular NO system through, on the one hand, selective NOS isoform deletions in otherwise intact animals and, on the other hand, transgenic overexpression of recombinant NOS isoforms in hosts, using genetically engineered viral vectors [12]. In this light, Khurana and colleagues have recently carried out the first genetic modification of intact human cerebral arteries, demonstrating the functional benefit of adenovirus-mediated overexpression of eNOS in these vessels [13]. Taken together, these findings not only unequivocally establish the presence of a NO system in the cerebral vasculature, but also indicate that NO is a prime active modulator of CBF.

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Cure Your Yeast Infection For Good

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