Enhanced expression of inducible nitric oxide synthase may be responsible for altered vascular reactivity in streptozotocin-induced diabetic rats

Growing evidence indicates that enhanced generation or actions of nitric oxide (NO) are implicated in the pathogenesis of hypertension in spontaneously hypertensive rats and diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. We investigated whether inducible nitric oxide synthase (iNOS) expression in STZ-induced diabetic rats is responsible for the alterations of vascular reactivity. Diabetic state was confirmed 28 days after injection of STZ (i.p) in rats by measuring blood glucose. In order to evaluate whether short term (4 weeks) diabetic state is related with altered vascular reactivity caused by iNOS expression, isometric tension experiments were performed. In addition, plasma nitrite/nitrate (NOx) levels and expression of iNOS in the lung and aorta of control and STZ-treated rats were compared by using Griess reagent and Western analysis, respectively. Results indicated that STZ-treated rats increased the maximal contractile response of the aorta to phenylephrine (PE), and high K+, while the sensitivity remained unaltered. Endothelium-dependent relaxation, but not SNP-mediated relaxation, was reduced in STZ-treated rats. Plasma nitrite/nitrates are significantly increased in STZ-treated rats compared to controls. The malondialdehyde (MDA) contents of liver, serum, and aorta of diabetic rats were also significantly increased. Furthermore, nitrotyrosine, a specific foot print of peroxynitrite, was significantly increased in endothelial cells and smooth muscle layers in STZ-induced diabetic aorta. Taken together, the present findings indicate that enhanced release of NO by iNOS along with increased lipid peroxidation in diabetic conditions may be responsible, at least in part, for the augmented contractility, possibly through the modification of endothelial integrity or ecNOS activity of endothelium in STZ-diabetic rat aorta.

Central Neural Pathway for the Rat Tongue / 대한해부학회지

Bartha strain of pseudorabies virus[PRV-Ba] was utilized as a tracer to identify the neuronal axis of rat tongue muscles ; intrinsic muscles and extrinsic muscles, styloglossus, genioglossus, and hyoglossus muscle. After injection of 10 microliter of PRV-Ba into tongue muscles and 48-96 hours survivals, rats were perfused with 4% paraformaldehyde lysine periodate and brains were removed. PRV-Ba were localized in neural circuits by immunohistochemistry employing rabbit anti PRV-Ba as a primary antibody and ABC method. Injection of PRV-Ba into the tongue muscles resulted in uptake and retrograde transport of PRV-Ba in the rat brain. The result showed a circuit specific connection of many nerve cell groups along the time sequence : PRV-Ba immunoreactive cells appeared in hypoglossal nucleus and motor trigeminal nucleus ipsilaterally as seen with conventional tracers. Raphe nucleus, prepositus hypoglossal nucleus, spinal trigeminal nucleus, Al, A5 and facial nucleus of rhombencephalon showed immunoreactivity bilaterally. There were positive neurons in parabrachial nucleus, locus ceruleus, mesencephalic trigeminal nucleus, periaqueductal gray and A7 of mesencephalon and paraventricular nucleus, suprachiasmatic nucleus, organum vasculosum of lamina terminalis of diencephalon. Also positive reactions were showed in amygdala, insular cortex, frontal cortex and subfornical organ in telencephalon. Early immunoreactivity was appeared in hypoglossal nucleus and motor trigeminal nucleus, and there were positive neurons in the nuclei of the medulla oblongate, midbrain, pons, hypothalamus, cerebellum and medial preoptic area at middle stage. Subsequently the viral antigens were found in forebrain cell groups, paraventricular nuclei, suprachiasmatic nucleus, lateral hypothalamic area and primary motor cortex in frontal lobe bilaterally at 80-90hrs postinjection. These data demonstrate that the PRV-Ba can across synapses in the central nervous system with projection specific pattern, and this virus defines many elements of the neural network governing tongue. Therefore PRV-Ba are proved as a excellent neurotracer in the tract-tracing researches.