BORDERLINE HYPERTENSIVE AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE PATIENTS HAVE ENHANCED PRODUCTION OF RENAL DOPAMINE - NORMALIZATION OFRENAL HEMODYNAMICS BY DOPA INFUSION

Background. In autosomal dominant polycystic kidney disease (ADPKD) th e pathophysiology of hypertension, which is frequently observed before loss of renal function, is not well understood. We investigated intra renal dopamine, the renin-angiotensin-aldosterone system (RAAS), and p lasma endothelin in relation to sodium homeostasis as potential hypert ensive factors in this disease. Methods. Eight borderline hypertensive ADPKD patients with (near) normal renal function and seven matched he althy control subjects were investigated at three levels of daily diet ary sodium intake: 150, 50 and 450 mmol. In the 450-mmol sodium intake period we studied the effects of renally formed dopamine by infusing its precursor DOPA (DOPA(i.v.), 7 mu g kg(-1) min(-1)). In the 50-mmol sodium intake period we studied the influence of the RAAS by administ ering enalaprilate (42 mu g kg(-1)), followed by angiotensin II (12 ng kg(-1) min(-1)) intravenously. GFR and ERPF were measured by continuo us infusion of inulin and PAH. Results. At all levels of sodium intake sodium balances were equal, but daily urinary excretions of dopamine and DOPA were higher (P<0.01) in the ADPKD patients than in the contro ls. Renal vascular resistance, filtration fraction and blood pressure were higher in the ADPKD patients (all P<0.05) while plasma renin acti vity was similar. DOPA(i.v.) normalized renal haemodynamics and increa sed plasma endothelin in ADPKD patients (all P<0.05), while stimulatio n of natriuresis was equal in both groups. Enalaprilate increased plas ma endothelin in the ADPKD patients and only partially normalized rena l haemodynamics. Conclusions. In borderline hypertensive ADPKD patient s: (1) urinary dopamine excretion is increased at all levels of sodium intake, suggesting that this may be needed to maintain sodium balance ; (2) stimulation of renal dopamine production is able to normalize re nal haemodynamics, making dopamine receptor agonism a potential therap eutic option; (3)the activity of the RAAS is not clearly enhanced; (4) renal vasodilatation increases plasma endothelin levels.