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In this study, we hypothesized that blunting of the natriuresis response to intracerebroventricularly (ICV) microinjected adrenergic agonists is involved in the development of hypertension in maternal low-protein intake (LP) offspring. A stainless steel cannula was stereotaxically implanted into the right lateral ventricle (LV), then we evaluated the ICV administration of adrenergic agonists at increasing concentrations, and of α1 and α2-adrenoceptor antagonists on blood pressure and urinary sodium handling in LP offspring relative to an age-matched normal-protein intake (NP) group. We confirmed that epinephrine (Epi) microinjected into the LV of conscious NP rats leads to enhanced natriuresis followed by a reduction in arterial pressure. This response is associated with increased proximal and post-proximal sodium excretion accompanied by an unchanged glomerular filtration rate. The current study showed, in both NP and LP offspring, that the natriuretic effect of Epi injection into the LV was abolished by prior local microinjection of an α1-adrenoceptor antagonist (prazosin). Conversely, LV α2-adrenoceptor antagonist (yohimbine) administration potentiated the action of Epi. The LV yohimbine pretreatment normalized urinary sodium excretion and reduced the blood pressure in LP compared with age-matched NP offspring. These are, as far as we are aware, the first results showing the role of central adrenergic receptors' interaction on hypertension pathogenesis in maternal LP fetal-programming offspring. This study also provides good evidence for the existence of central nervous system adrenergic mechanisms consisting of α1 and α2-adrenoceptors, which work reciprocally on the control of renal sodium excretion and blood pressure. Although the precise mechanism of the different natriuretic response of NP and LP rats is still uncertain, these results lead us to speculate that inappropriate neural adrenergic pathways might have significant effects on tubule sodium transport, resulting in the inability of the kidneys to control hydrosaline balance and, consequently, an increase in blood pressure.

biology open

Effect of intracerebroventricular epinephrine microinjection on blood pressure and urinary sodium handling in gestational protein-restricted male adult rat offspring