Background: Progression of Chronic kidney disease (CKD) may result from tissue hypoxia induced by small artery structural narrowing, with increased renal vascular resistance (RVR) and impaired blood supply. We investigated whether vasodilating therapy (VT) is superior to non-vasodilating therapy (nonVT) for improvement of RVR, tissue oxygenation, and preservation of kidney function. Methods: Eighty-two hypertensive grade 3-4 CKD patients (glomerular filtration rate (GFR) 36±15 ml/min/1.73 m2) were randomised to renin-angiotensin inhibition combined with either VT (amlodipine) or nonVT (beta-blocker metoprolol). At baseline and following 18 months of therapy we determined forearm resistance by venous occlusion plethysmography. Using magnetic resonance imaging (MRI) renal artery blood flow was measured for calculation of RVR, and blood oxygen level dependent (BOLD) MRI was used as a marker of renal oxygenation (R2*). GFR was measured as 51Cr-EDTA clearance. Results: The VT and nonVT arms had similar blood pressure levels throughout the study. At follow-up, in the VT group forearm resting resistance had decreased by 7% (P<0.05) and RVR by 12% (P<0.05), while in the nonVT group forearm resistance increased by 39% (P<0.01) while RVR remained unchanged. Cortical and medullary R2* values were not affected by VT and nonVT. After 18 months GFR decline was similar in the two groups (3.0 vs. 3.3 ml/min/1.73 m2). Conclusions: In CKD, long-term VT reduced both peripheral and RVR, but was not associated with improved renal oxygenation and did not influence loss of kidney function compared to nonVT