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  • LY341495 In essential hypertensive patients it


    In essential hypertensive patients, it is known that the CB is enlarged (Habeck, 1986). In addition to morphological changes in the CB, hyperventilation was reported in essential hypertensive patients at resting conditions (Trzebski et al., 1982). Furthermore, CB is innervated by postganglionic sympathetic nerve from the superior cervical ganglion (Verna et al., 1984) and an elevated level of sympathetic nerve activity was observed in the patients (Anderson et al., 1989, Grassi et al., 1998, Grassi et al., 2000). These previous studies imply that alteration in chemoreceptor reflex under hypertensive conditions is attributable to the changes in CB, including morphological changes. Spontaneously hypertensive rat (SHR) strains are animal models of essential hypertension and are used to study the pathophysiology of essential hypertension. It has been reported that the volume of CB in SHR strains is increased compared with that of age-matched genetically comparable Wistar Kyoto rats (WKY) (Alho et al., 1984). In addition to the morphological changes, it has also been reported that dopamine (DA) content was similar but noradrenaline (NA) content was increased by 50% in the CB of the New Zealand strain of hypertensive rat compared with those of normotensive rat (Pallot and Barer, 1985). It is generally known that DA and NA are present in glomus LY341495 (Gonzalez et al., 1994) and are inhibitory neuromodulators in CB chemotransduction via dopaminergic D2 receptor and adrenergic α2 receptor, respectively (Nurse, 2005, Lahiri et al., 2006). Therefore, there is the possibility that the signal transduction from CB to the nucleus of the solitary tract is regulated by the inhibitory NA in SHR strains.
    Materials and methods
    Discussion In the present study, it was revealed that CB of SHR/Izm is enlarged in size as shown in the three-dimensional image. Moreover, apparent vasodilatation could not be observed in the CB of SHR/Izm. These results are supported by the report that the diameter of blood vessels within CB in SHR strains is similar to that in WKY strains (Takahashi et al., 2011). It is generally accepted that chronic hypoxia (10% O2) causes the enlargement of the CB with vasodilatation (Wang and Bisgard, 2002, Kusakabe et al., 2005). Interestingly, it was reported that chronic hypercapnic hypoxia (10% O2, 6–7% CO2) caused the enlargement of the rat CB without vasodilatation within the CB (Kusakabe et al., 2005). Thus, between SHR/Izm and hypercapnic hypoxic rats, there are similarities in the volume and the diameter of blood vessels in the CB. It was reported that renal sympathetic nerve activity is increased when rats are exposed to hypercapnic hypoxia (Hirakawa et al., 1997). Given this finding, it is suggested that sympathetic nerve input from superior cervical ganglion is increased, thereby inducing vasoconstriction within the CB of hypercapnic hypoxic rats. Therefore, in hypercapnic hypoxic rats, the enlargement of the CB would be caused by the effect of hypoxia and vasodilatation would be inhibited by the effect of increased sympathetic nerve activity. On the other hand, previous electrophysiological studies showed that sympathetic nerve activity was also increased in SHR strains compared with that in WKY strains (Judy and Farrell, 1979, Lundin et al., 1984, Sugimura et al., 2008). Given this finding, it is suggested that increased sympathetic activity causes vasoconstriction within the CB of SHR/Izm as in the case of the hypercapnic hypoxic rats, leading to reduction in blood supply to the CB. As a result of the decreased blood supply, the CB of SHR/Izm would be rendered regional hypoxia and become enlarged without vasodilatation. Therefore, the morphology of the CB would be similar between SHR/Izm and hypercapnic hypoxic rats due to the effect of hypoxia and the increased sympathetic nerve activity. It has been reported by immunohistochemistry that chronic hypoxia enhances the immunoreactivity for TH in the CB (Wang et al., 1998, Wang and Bisgard, 2002, Hui et al., 2003). Although it is suggested that the CB of SHR/Izm is rendered regional hypoxia as mentioned earlier, immunoreactivity for TH in CB was similar between SHR/Izm and WKY/Izm in the present study. Therefore, it might be that the regional hypoxic condition in the CB under hypertension is slightly different from the systemic hypoxic condition under environmental hypoxia. On the other hand, the present immunohistochemical study showed that DBH immunoreactivity is enhanced in glomus cells of SHR/Izm. Considering the previous report that NA content was increased in the CB of the New Zealand strain of hypertensive rat (Pallot and Barer, 1985), it is suggested that NA biosynthesis is facilitated in glomus cells of CB in SHR/Izm. It has been suggested that NA in glomus cells, along with DA, is inhibitory to CB activity and is neuromodulator in signal transduction from CB to the nucleus of the solitary tract (Kou et al., 1991, Almaraz et al., 1997, Overholt and Prabhakar, 1999). Furthermore, it has been reported that CSN discharge of SHR strains under normoxic conditions is not different from that of normotensive rats (Fukuda et al., 1987). Therefore, in SHR/Izm, it is suggested that DBH is increased in glomus cells in order to synthesize NA, and furthermore to maintain the CSN discharge at a normal level by the inhibitory NA. Moreover, it is reported that minute ventilation under air-breathing conditions is not different between SHR strains and WKY rat strains (Grisk et al., 1996). Thus, in SHR/Izm, normal respiration under resting conditions would be attributable to the normal CSN activity modulated by the effect of NA in addition to DA.