Borderline hypertensive autosomal dominant polycystic kidney disease patients have enhanced production of renal dopamine. Normalization of renal haemodynamics by DOPA infusion.
BACKGROUND
In autosomal dominant polycystic kidney disease (ADPKD) the pathophysiology of hypertension, which is frequently observed before loss of renal function, is not well understood. We investigated intrarenal dopamine, the renin-angiotensin-aldosterone system (RAAS), and plasma endothelin in relation to sodium homeostasis as potential hypertensive factors in this disease.


METHODS
Eight borderline hypertensive ADPKD patients with (near) normal renal function and seven matched healthy control subjects were investigated at three levels of daily dietary 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 (DOPAi.v., 7 micrograms kg-1 min-1). In the 50-mmol sodium intake period we studied the influence of the RAAS by administering enalaprilate (42 micrograms kg-1), followed by angiotensin II (12 ng kg-1 min-1) intravenously. GFR and ERPF were measured by continuous 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 controls. Renal vascular resistance, filtration fraction and blood pressure were higher in the ADPKD patients (all P < 0.05) while plasma renin activity was similar. DOPAi.v. normalized renal haemodynamics and increased plasma endothelin in ADPKD patients (all P < 0.05), while stimulation of natriuresis was equal in both groups. Enalaprilate increased plasma endothelin in the ADPKD patients and only partially normalized renal haemodynamics.


CONCLUSIONS
In borderline hypertensive ADPKD patients: (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 renal haemodynamics, making dopamine receptor agonism a potential therapeutic option; (3) the activity of the RAAS is not clearly enhanced; (4) renal vasodilatation increases plasma endothelin levels.
Barendregt
J N
JN
Department of Nephrology, University Hospital Leiden, The Netherlands.
Florijn
K W
KW
Muizert
Y
Y
Chang
P C
PC
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D004295:Dihydroxyphenylalanine / Q000627:therapeutic use*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000627:therapeutic use*; D015773:Enalaprilat / Q000008:administration & dosage; D016232:Endothelins / Q000097:blood / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage
D000806:Angiotensin-Converting Enzyme Inhibitors; D015259:Dopamine Agents; D016232:Endothelins; D012982:Sodium, Dietary; D000804:Angiotensin II; D000450:Aldosterone; D004295:Dihydroxyphenylalanine; D012964:Sodium; D015773:Enalaprilat; D004298:Dopamine