BORDERLINE HYPERTENSIVE AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE PATIENTS HAVE ENHANCED PRODUCTION OF RENAL DOPAMINE - NORMALIZATION OFRENAL HEMODYNAMICS BY DOPA INFUSION
Jnm. Barendregt et al., BORDERLINE HYPERTENSIVE AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE PATIENTS HAVE ENHANCED PRODUCTION OF RENAL DOPAMINE - NORMALIZATION OFRENAL HEMODYNAMICS BY DOPA INFUSION, Nephrology, dialysis, transplantation, 10(8), 1995, pp. 1332-1341
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.