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Amlodipine Improves Vessel Function and Remodeling in the Lewis Polycystic Kidney Rat Mesenteric Artery
Ko Jin Quek1, Omar Z Ameer1,2, Jacqueline K Phillips1
1Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
Insights
L-type Ca2+ channel blockers like amlodipine improve vascular function in chronic kidney disease (CKD) rats. While improving blood pressure and some vessel structure, artery wall thickness remained elevated in hypertensive CKD rats.
Area of Science:
- Cardiovascular Research
- Nephrology
- Pharmacology
Background:
- Hypertension is a common comorbidity in chronic kidney disease (CKD).
- L-type Ca2+ channel (LTCC) blockers are frequently used to manage hypertension in CKD patients.
- The Lewis Polycystic Kidney (LPK) rat serves as a genetic model for hypertension and CKD.
Purpose of the Study:
- To investigate the long-term effects of LTCC blockade on resistance vasculature in a rat model of CKD.
- To assess the impact of amlodipine treatment on vascular structure and function in LPK rats.
Main Methods:
- Mixed-sex LPK and Lewis control rats were treated with amlodipine or vehicle from 4 to 18 weeks of age.
- Systolic blood pressure and renal function were assessed.
- Mesenteric vasculature was analyzed for functional and structural changes using pressure myography and histology.
Main Results:
- Amlodipine treatment significantly reduced blood pressure and plasma creatinine in LPK rats.
- Vascular structural improvements were observed, including changes in diameter and wall-lumen ratio, though wall thickness remained elevated.
- Treatment ameliorated endothelial dysfunction and improved nitric oxide-dependent and endothelium-derived hyperpolarization vasorelaxation.
Conclusions:
- LTCC blockade with amlodipine partially improves detrimental structural and functional vascular alterations in resistance arteries of CKD rats.
- Despite improvements, some vascular structural abnormalities persist in LPK rats even with amlodipine treatment.
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.
