Amlodipine Improves Vessel Function and Remodeling in the Lewis Polycystic Kidney Rat Mesenteric Artery

Abstract

Background: Hypertension is a common comorbidity associated with chronic kidney disease (CKD). Treatment in these patients often involves L-type Ca2+ channel (LTCC) blockers. The effect of chronic LTCC-blockade treatment on resistance vasculature was investigated in a genetic hypertensive rat model of CKD, the Lewis Polycystic Kidney (LPK) rat.

Methods: Mixed-sex LPK and Lewis control rats (total n = 38) were allocated to treated (amlodipine 20 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups. Following systolic blood pressure and renal function assessment, animals were euthanized and mesenteric vasculature was collected for functional and structural assessment using pressure myography and histology.

Results: Amlodipine treatment reduced LPK rat blood pressure (untreated vs. treated: 185 ± 5 vs. 165 ± 9 mm Hg; P = 0.019), reduced plasma creatinine (untreated vs. treated: 197 ± 17 vs. 140 ± 16 µmol/l; P = 0.002), and improved some vascular structural parameters (internal and external diameters and wall-lumen ratios); however wall thickness was still increased in LPK relative to Lewis despite treatment (Lewis vs. LPK: 31 ± 2 vs. 41 ± 2 µm, P = 0.047). Treatment improved LPK rats' endothelium dysfunction, and nitric oxide-dependent and endothelium-derived hyperpolarization vasorelaxation components, and downregulated prostanoid contributions. LTCC blockade had no effect on biomechanical properties of compliance and intrinsic stiffness, nor artery wall composition.

Conclusions: Our results indicate that blockade of LTCCs with amlodipine is effective in improving, to a certain extent, detrimental structural and functional vascular features of resistance arteries in CKD.

Keywords: blood pressure; calcium channel blockade; chronic kidney disease; endothelial function; hypertension; mesenteric resistance artery; vascular stiffness.