Sympathetic Activity in Dahl Salt-Sensitive Hypertension - Why is a Nitric Oxide-Induced Inhibitory System Up-Regulated in the Sympathetic Center?

Nishida, Yasuhiro

doi:10.4172/2161-0959.1000131

Cited by 2 publications

(1 citation statement)

References 47 publications

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“…Cumulative research over an extensive time span will be necessary to elucidate the changes induced in long-term mechanisms of blood-pressure regulation [ 38 – 40 ] and short-term circulatory functions by these effects of +Gz load and the trained G-load tolerance. Understanding endogenous physiological responses will in turn provide new information and materials leading to further investigations.…”

Section: Discussionmentioning

confidence: 99%

Effects and biological limitations of +Gz acceleration on the autonomic functions-related circulation in rats

Nishida

Maruyama²,

Shouji

et al. 2016

J Physiol Sci

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The effects of gravitational loading (G load) on humans have been studied ever since the early 20th century. After the dangers of G load in the vertical head-to-leg direction (+Gz load) became evident, many animal experiments were performed between 1920 and 1945 in an effort to identify the origins of high G-force-induced loss of consciousness (G-LOC), which led to development of the anti-G suit. The establishment of norms and training for G-LOC prevention resulted in a gradual decline in reports of animal experiments on G load, a decline that steepened with the establishment of anti-G techniques in humans, such as special breathing methods and skeletal muscle contraction, called an anti-G straining maneuver, which are voluntary physiological functions. Because the issue involves humans during flight, the effects on humans themselves are clearly of great importance, but ethical considerations largely preclude any research on the human body that probes to any depth the endogenous physiological states and functions. The decline in reports on animal experiments may therefore signify a general decline in research into the changes seen in the various involuntary, autonomic functions. The declining number of related reports on investigations of physiological autonomic systems other than the circulatory system seems to bear this out. In this review, we therefore describe our findings on the effects of G load on the autonomic nervous system, cardiac function, cerebral blood flow, tissue oxygen level, and other physiological autonomic functions as measured in animal experiments, including denervation or pharmacological blocking, in an effort to present the limits and the mechanisms of G-load response extending physiologically. We demonstrate previously unrecognized risks due to G load, and also describe fundamental research aimed at countering these effects and development of a scientific training measure devised for actively enhancing +Gz tolerance in involuntary, autonomic system functions. The research described here is rough and incomplete, but it is offered as a beginning, in the hope that researchers may find it of reference and carry the effort toward completion. The advances described here include (1) a finding that cerebral arterial perfusion pressure decreases to nearly zero under +5.0 Gz loads, (2) indications that G load may cause myocardial microinjuries, (3) detection of differences between cerebral regions in tissue-oxygen level under +3.0 Gz load, (4) discovery that hypotension is deeper under decreasing +Gz loads than increasing +Gz loads with use of an anti-G system, due in part to suppression of baroreceptor reflex, and (5) revelations and efforts investigating new measures to reduce cerebral hypotension, namely the “teeth-clenching pressor response” and preconditioning with slight but repeated G loads.

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Section: Discussionmentioning

confidence: 99%

Effects and biological limitations of +Gz acceleration on the autonomic functions-related circulation in rats

Nishida

Maruyama²,

Shouji

et al. 2016

J Physiol Sci

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Sympathetic Regulation of the NCC (Sodium Chloride Cotransporter) in Dahl Salt–Sensitive Hypertension

et al. 2020

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Increased sympathoexcitation and renal sodium retention during high salt intake are hallmarks of the salt sensitivity of blood pressure. The mechanism(s) by which excessive sympathetic nervous system release of norepinephrine influences renal sodium reabsorption is unclear. However, studies demonstrate that norepinephrine can stimulate the activity of the NCC (sodium chloride cotransporter) and promote the development of SSH (salt-sensitive hypertension). The adrenergic signaling pathways governing NCC activity remain a significant source of controversy with opposing studies suggesting a central role of upstream α 1 - and β-adrenoceptors in the canonical regulatory pathway involving WNKs (with-no-lysine kinases), SPAK (STE20/SPS1-related proline alanine-rich kinase), and OxSR1 (oxidative stress response 1). In our previous study, α 1 -adrenoceptor antagonism in norepinephrine-infused male Sprague-Dawley rats prevented the development of norepinephrine–evoked SSH in part by suppressing NCC activity and expression. In these studies, we used selective adrenoceptor antagonism in male Dahl salt–sensitive rats to test the hypothesis that norepinephrine-mediated activation of the NCC in Dahl SSH occurs via an α 1 -adrenoceptor dependent pathway. A high-salt diet evoked significant increases in NCC activity, expression, and phosphorylation in Dahl salt–sensitive rats that developed SSH. Increases were associated with a dysfunctional WNK1/4 dynamic and a failure to suppress SPAK/OxSR1 activity. α 1 -adrenoceptor antagonism initiated before high–salt intake or following the establishment of SSH attenuated blood pressure in part by suppressing NCC activity, expression, and phosphorylation. Collectively, our findings support the existence of a norepinephrine-activated α 1 -adrenoceptor gated pathway that relies on WNK/SPAK/OxSR1 signaling to regulate NCC activity in SSH.

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Sympathetic Activity in Dahl Salt-Sensitive Hypertension - Why is a Nitric Oxide-Induced Inhibitory System Up-Regulated in the Sympathetic Center?

Cited by 2 publications

References 47 publications

Effects and biological limitations of +Gz acceleration on the autonomic functions-related circulation in rats

Effects and biological limitations of +Gz acceleration on the autonomic functions-related circulation in rats

Sympathetic Regulation of the NCC (Sodium Chloride Cotransporter) in Dahl Salt–Sensitive Hypertension

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