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.
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 hypertensiveADPKDpatients 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 ADPKDpatients than in the controls. Renal vascular resistance, filtration fraction and blood pressure were higher in the ADPKDpatients (all P < 0.05) while plasma renin activity was similar. DOPAi.v. normalized renal haemodynamics and increased plasma endothelin in ADPKDpatients (all P < 0.05), while stimulation of natriuresis was equal in both groups. Enalaprilate increased plasma endothelin in the ADPKDpatients and only partially normalized renal haemodynamics. CONCLUSIONS: In borderline hypertensiveADPKDpatients: (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.
Authors: Sarmed H Kathem; Ashraf M Mohieldin; Shakila Abdul-Majeed; Sajida H Ismail; Qaiss H Altaei; Ibrahim K Alshimmari; Mohanned M Alsaidi; Hussein Khammas; Andromeda M Nauli; Bina Joe; Surya M Nauli Journal: J Geriatr Cardiol Date: 2014-03 Impact factor: 3.327