Hypothalamic Neuronal Nitric Oxide Synthase With Essential Hypertension Related

Objectives: 1. To elucidate the relation between neuronal nitric oxide synthase (nNOS) and the essential hypertension (EH) pathogenesis, we investigated the distribution of nNOS positive neurons and the expression of nNOS in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) in spontaneously hypertensive rats (SHR) of different week age. 2. To further explore the potential roles of nNOS in the EH and provide experimental and theoretical evidence for the central mechanism of prazosin (α1 adrenergic receptor blocker) in EH therapy, we observed the distribution of nNOS positive neurons and the expression of nNOS in the PVN and SON in SHR administered prazosin for one month.Materials and Methods: 1. Male SHR aged 4～24 weeks were used and divided by week age into 4 groups: 4, 8, 12 and 24 week group, compared to age-matched Wistar rats. Then nNOS immunofluorescence staining combined with photomicrographs analysis technique was performed to detect the distribution of nNOS positive neurons and the expression of nNOS in the PVN and SON in these rats. Besides, nNOS western blot detection was performed to examine the protein levels of nNOS in the hypothalamus in these rats. 2. Male SHR aged 8 weeks were exposed to oral administration of prazosin for one month (SHRp). The differences in mean artery pressure (MAP), heart rate (HR) and renal histochemical staining as well as in the distribution of nNOS positive neurons and the expression of nNOS in the PVN and SON were compared in age-matched SHRp, untreated SHR and normal Wistar rats.Results: 1. Along with the week age and blood pressure increasing, the number of nNOS positive neurons in the PVN and SON and the protein levels of nNOS in the hypothalamus increased in normal Wistar rats, but the parameters showed no obvious changes in SHR. Compared with age-matched Wistar rats, the above parameters in SHR significantly reduced. 2. Compared with untreated SHR, SHRp showed significantly lower blood pressure and attenuated renal fibrosis. Furthermore, in the PVN and SON, SHRp exhibited increases in the numbers of nNOS positive neurons and the nNOS protein levels. However, all of the above paratmaters didn't reach the normal levels in Wistar rats.Conclusions: 1. In SHR, nNOS in the PVN and SON may contribute to hypertension pathogenesis and play a vital role in EH development. 2. Prasozin may play central depressive role in hypertension by regulating nNOS in the PVN and SON and then partly reverse the process of EH.