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

Abstract

Background. In this study, we hypothesized that blunting of the natriuresis response to intracerebroventricularly (i.c.v.) microinjected adrenergic agonists are involved in the development of hypertension in maternal low-protein (LP) intake offspring. Methods. Stainless steel cannula was stereotaxically implanted into the right lateral ventricle, by use of techniques reported elsewhere and after that, was evaluated the effect of i.c.v. injection 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 age-matched, normal (NP) protein intake group. Results. We confirmed that epinephrine (Epi) microinjected into the lateral ventricle (LV) of conscious NP rats leads to enhanced natriuresis followed by a reduction in arterial pressure. This response was 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 natriuretic effect of Epi injection into the LV was abolished by prior local microinjection of an α1adrenoceptor antagonist (prazosin). Conversely, LV α2-adrenoceptor antagonist (yohimbine) administration potentiated the action of epinephrine. The LV yohimbine pretreatment normalized urinary sodium excretion and reduced the blood pressure in LP compared with age-matched NP offspring. Conclusion. These are, as far as we are aware, the first results showing the role of central adrenergic receptors interaction on hypertension pathogenesis in maternal protein-restricted fetal programming offspring. The study also provides good evidence of the existence of central nervous system adrenergic mechanisms consisting of α1 and α2-adrenoceptors, which works 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 led 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.3