Endocrine regulation of osmotic stability and blood volume and, hence arterial pressure are mediated by the antidiuretic hormone vasopressin (VP), which is synthesised in SON and PVN magnocellular neurones (MCNs) then transported via axonal projections to the PP, where biologically active VP is stored until mobilised for secretion into the circulation by MCN electrical activities evoked by hyperosmolality. A rise in plasma osmolality is detected by intrinsic MCN osmoreceptor mechanisms and by specialised osmosensitive neurones in the circumventricular organs (CVOs) that project to, and regulate, SON MCNs (e.g, SFO). Upon release, VP travels through the blood stream to specific receptor targets located in the kidney where it increases the permeability of the collecting ducts to water, reducing the renal excretion of water, thus promoting water conservation and increasing blood volume. It is known that spontaneously hypertensive rats (SHRs) drink more water than normotensive Wistar Kyoto rats (WKYs), show hypertrophy of the PP along with a higher PP VP content and elevated plasma VP levels. Evidence suggests that these are primary abnormalities in the SHR, not secondary to the hypertension. Whilst the SON is a homogenous collection of MCNs, the PVN is divided into a lateral and more medial sub-division of MCNs and smaller parvocellular neurones respectively. Through descending projections from parvocellular neurones to the brainstem, notably the RVLM and intermediolateral cell column of the spinal cord, the PVN regulates changes in sympathetic nerve activity involved in the regulation of both arterial pressure and blood volume. Interestingly, the PVN excitatory drive to the RVLM appears to be heightened in the SHR compared to the normotensive WKY. Correspondingly, GABA drive in PVN is decreased in hypertensive models.
The AP is a brainstem curcumventricular organ (CVO), a structure characterized by small, high permeability fenestrated capillaries that permits substances that do not cross the blood brain barrier to trigger changes in brain function. The AP has been implicated in the central regulation of the cardiovascular system. An intact AP appears necessary for angiotensin II-induced hypertension and lesioning of the AP attenuates hypertension in the SHR. The RVLM is a key region for arterial pressure homeostasis. Indeed, its acute bilateral destruction causes blood pressure to fall to levels seen after spinal section. It is a major site of pre-motor sympathetic bulbospinal neurones innervating pre-ganglionic sympathetic motoneurones in the inter-mediolateral cell column of the spinal cord. Indeed, much of the sympathetic tone destined for the heart and arterioles is generated in the RVLM and is under powerful baroreceptor reflex modulation. This region also mediates many sympathoexcitatory reflex responses. In addition, it plays a major role in mediating sympathoexcitatory responses that are evoked from supra-medullary structures such as the PVN. In the SHR, there appears to be an enhanced descending glutamatergic drive to preganglionic motoneurones compared to WKY. This could reflect an enhanced glutamatergic drive to RVLM neurones that may, in part, be dependent upon increased PVN activity. Lesioning of the NTS results in fulminating hypertension subsequent pulmonary oedema and death in rats. Recently, selective electrical silencing of genetically targeted catecholaminergic neurones in NTS chronically reset arterial pressure to higher levels in the SHR relative to the WKY rat. Thus, the NTS exerts a braking influence on sympathetic pre-motor activity, which appears more pronounced in the SHR. Importantly the NTS is the site of termination of visceral cardiovascular afferents, including baroreceptors. OC, optic chiasm.
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