Hypothalamic Nitric Oxide Role In The Regulation Of Vasopressin Secretion And Its Correlation With Essential Hypertension Research

Part 1 Nitric oxide mediates feedback inhibition in angiotensinâ…¡-induced upregulation of vasopressin mRNAAngiotensinâ…¡(Angâ…¡) stimulates hypothalamic magnocellular neurons to release arginine vasopressin (AVP) via Angâ…¡type 1 receptors (AT-1R) during chronic hyperosmotic condition. On the other hand, endogenous nitric oxide (NO) tonically inhibits the activity of AVP producing neurons; and system infusion of Angâ…¡elicits the activity of NO producing neruons in the hypothalamus. These studies suggest that NO may mediate feedback inhibition in Angâ…¡-induced AVP secretion.To confirm this hypothesis, we first investigated colocalization of neuronal NO synthase (nNOS) and AT-1R in the hypothalamic magnocellular nuclei of adult male rats by using double immunofluorescence. We found that 60% and 65% of AT-1R immunoreactive neurons coexpressed nNOS in the hypothalamic paraventricular nucleus and supraoptic nucleus, respectively. We then demonstrated that intracerebroventricular administration of NOS inhibitor N-Omega-Nitro-L-arginine methyl ester further enhanced upregulation of AVP mRNA level but totally abolished upregulation of nNOS mRNA level induced by a prior administration of Angâ…¡into the lateral ventricle of anesthetized rats. These morphological and pharmacological data suggest that NO mediates negative feedback regulation of Angâ…¡induced AVP secretion. Part 2 Distribution and the coexpression of neuronal nitric oxide synthase and angiotensinâ…¡type 1 receptor in the hypothalamic neurons in hypertension conditionPhysiological researches suggest that peripheral and central renin-angiotensin systems (RAS) are both in activated state in hypertensive condition. Especially the increase of endogenous angiotensinâ…¡(Angâ…¡) and angiotensinâ…¡type 1 receptors (AT-1R) can promote central arginine vasopressin (AVP) in the hypothalamus to release to periphery. On the other hand, central endogenous nitric oxide (NO) regulates cardiovascular activity and blood pressure by inhibiting central sympathetic and modulating AVP activity. In our prvious experiment, we have proved that NO mediates negative feedback regulation of Angâ…¡induced AVP secretion. However, whether there exists the increase of expression of nNOS and further inhibites the activity of RAS in hypertensive condition remains to be determined.In order to further explore the potential role of NO in the essential hypertension (EH), we first investigated colocalization of neuronal NO synthase (nNOS) and AT-1R positive neurons in the hypothalamic nuclei of Wistar-Kyoto (WKY) rats and spontaneously hypertansive rat (SHR) by dualimmunofluorescence staining. We found there are a quantity of nNOS and AT-1R immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). The number of nNOS and AT-1R positive neurons of SHR are both more than that of WKY;the ratios of coexistence varied in hypothalamus of SHR and WKY rats, and the ratio of coexistence of SHR is higher than WKY rats. Second, we found that the nNOS mRNA and AVP mRNA levels are upregulated in SHR group by RT-PCR technology. Thus, we conclude that NO might act as an inhibitory regulator of the activity of RAS in response to hypertension.