Brain Gαi2-subunit proteins and the prevention of salt sensitive hypertension

摘要: To counter the development of salt-sensitive hypertension multiple brain G-protein–coupled receptor (GPCR) systems are activated to facilitate sympathoinhibition, sodium homeostasis and normotension. Currently there is a paucity knowledge regarding role down-stream GPCR-activated Gα-subunit proteins in these critically important physiological regulatory responses required for long-term blood pressure regulation. We have determined that Gαi2-proteins mediate natriuretic sympathoinhibitory produced by acute pharmacological (exogenous central nociceptin/orphanin FQ α2-adrenoceptor activation) challenges (intravenous volume expansion 1M load) conscious Sprague-Dawley rats. demonstrated salt-resistant rat phenotypes, high dietary salt intake evokes site-specific up-regulation hypothalamic paraventricular nucleus (PVN) Gαi2–proteins. Further, we established PVN Gαi2 protein prevents of, renal nerve-dependent sympathetically mediated Dahl Additionally, failure up-regulate during salt-intake contributes pathophysiology hypertension. Collectively, our data demonstrate brain, likely specific, pathways represent molecular pathway mediating renal-nerve dependent evoked maintain phenotype. impairment this endogenous “anti-hypertensive” mechanism