Losartan normalizes blood pressure and prevents renal damage and inflammation induced by fructose overload. l-dopa/dopamine index as a new potential biomarker of renal damage

PUYÓ AM; RUKAVINA MIKUSIC NL; KOUYOUMDZIAN NM; DEL MAURO J; CAO G; PANDOLFO M; GIRONACCI MM; TOBLLI JE; FERNÁNDEZ BE; CHOI MR

Milán

Congreso; 28th European Meeting on Hypertension and Cardiovascular Protection; 2018

European Society of Hypertension

Introduction:The renin angiotensin system (RAS) and the renaldopaminergic system (RDS) act as autocrine and paracrine systems to regulaterenal sodium management and inflammation and their alterations have beenassociated to hypertension and renal damage. Nearly 30-50% of hypertensivepatients have insulin resistance (IR), which has a strong correlation withmicroalbuminuria. Objectives: Theaim was to evaluate the effects of RAS blockade with losartan on blood pressureand renal damage in a model of IR by fructose overload (FO), and itsassociation to changes in the RDS. Finally, we studied the behaviour of theurinary L-dopa/dopamine index as a potential biomarker of renal dysfunction. Design and methods: Male Sprague Dawleyrats were divided into: Control (C, tap water), FO (10% w/v of fructosesolution), Losartan (L, 30 mg/kg/day in tap water), FO+L (30 mg/kg/day infructose solution) groups for 4, 8 and 12 weeks. Systolic blood pressure (SBP)and metabolic parameters were measured. Urinary L-dopa and dopamine, diuresis,natriuresis and microalbuminuria were determined. Renal expression of D1receptor (D1R), pro-inflammatory markers (IL-6, TNF-α, TGF-β1, Ang II) andNa+,K+-ATPase expression and activity were determined. Results: Losartan prevented the increase in SBP and Na+,K+-ATPaseactivity and the reduction in natriuresis induced by FO from week 4 (p<0.05).Increased L-dopa/dopamine index and decreased D1R expression in FO rats wereprevented by losartan since week 4 (p<0.05). The same pattern was observedfor renal expression of Na+,K+-ATPase, IL-6, TNF-α and TGF-β1 since week 8(p<0.05), with no changes in Ang II. FO was associated with the appearanceof microalbuminuria at week 12, effect prevented by losartan (p<0.001). Conclusions: These results provide themechanisms by which a prohypertensive and proinflammatory system, such as RAS,downregulates another antihypertensive and antiinflammatory system such as RDS,establishing a positive feedback loop that leads to hypertension and kidney inflammationdue to FO. Furthermore, we demonstrated the potential usefulness of theL-dopa/dopamine index as a biochemical marker of renal dysfunction, earlierthan microalbuminuria, and as a predictor of response to treatment andfollow-up of hypertension and kidney damage.