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Published on: June 30, 2018
Evaluation of vascular function in apolipoprotein E knockout mice with angiotensin-dependent renovascular
Roberia M P Arruda1, Veronica A Peotta, Silvana S Meyrelles
1Laboratory of Transgenes and Cardiovascular Control, Biomedical Center, Federal University of Espirito Santo, Brazil.
Insights
This study shows that combined atherosclerosis and hypertension in mice leads to increased vascular reactivity and impaired endothelial function. These vascular changes contribute to maintaining high blood pressure in this combined disease model.
Area of Science:
- Cardiovascular Research
- Vascular Biology
- Hypertension Research
Background:
- Endothelial dysfunction is a hallmark of atherosclerosis and arterial hypertension.
- Angiotensin plays a significant role in both cardiovascular pathologies.
- Understanding the interplay between these conditions is crucial for developing effective treatments.
Purpose of the Study:
- To investigate vascular function in models of hypercholesterolemia/atherosclerosis and angiotensin II-dependent hypertension.
- To evaluate the combined effects of these conditions on vascular reactivity and endothelial function.
- To determine the contribution of vascular changes to hypertension maintenance.
Main Methods:
- Utilized apolipoprotein E knockout (apoE) and C57BL/6 mice.
- Induced hypertension using the 2-kidney 1-clip (2K1C) model or sham operation.
- Assessed vascular reactivity to norepinephrine, acetylcholine, and sodium nitroprusside in mesenteric arterioles.
- Measured mean arterial pressure and concentration-effect curves.
Main Results:
- Hypertension was confirmed in 2K1C models (apoE-2K1C and C57-2K1C).
- Vascular hyper-reactivity to norepinephrine was observed in all groups except C57-Sham mice.
- Endothelium-dependent relaxation to acetylcholine was significantly reduced in hypertensive groups (apoE-2K1C and C57-2K1C).
- Sodium nitroprusside-induced relaxation was similar across all groups, indicating preserved smooth muscle function.
Conclusions:
- In C57-2K1C mice, increased norepinephrine reactivity and reduced endothelium-dependent relaxation contribute to hypertension.
- Early-stage atherosclerosis in apoE mice shows norepinephrine hyper-reactivity but not yet endothelial dysfunction.
- The co-occurrence of atherosclerosis and hypertension did not result in additive detrimental effects on vascular function in this model.
Abstract:
It is known that the endothelial function is compromised in atherosclerosis and arterial hypertension and that angiotensin is an important factor contributing to both pathophysiologies. The aim of this study was to evaluate the vascular function in a hypercholesterolemia/atherosclerosis model, in the angiotensin II-dependent 2-kidney 1-clip (2K1C) hypertension model and when both conditions coexist. Eight-week-old apolipoprotein E knockout (apoE; n=20) and C57BL/6 (C57; n=20) mice underwent a 2K1C or sham operation and were studied 28 days later. Mean arterial pressure was higher in apoE-2K1C and C57-2K1C (126+/-3 and 128+/-3 mm Hg) when compared with the apoE-Sham and C57-Sham (103+/-2 and 104+/-2 mm Hg, respectively; P<0.05). The vascular reactivity to norepinephrine (NE; 10(-9) to 2 x 10(-3) mol/L), acetylcholine (ACh), and sodium nitroprusside (SNP; 10(-10) to 10(-3) mol/L) was evaluated in the mesenteric arteriolar bed through concentration-effect curves. NE caused vascular hyper-reactivity in apoE-Sham, apoE-2K1C, and C57-2K1C (maximal response 146+/-5, 144+/-5, and 159+/-4 mm Hg, respectively) compared with C57-Sham (122+/-7 mm Hg; P<0.05). The ACh-induced relaxation was smaller (P<0.05) in apoE-2K1C and C57-2K1C (maximal response 53+/-3% and 46+/-3%) than in apoE-Sham and C57-Sham mice (78+/-5% and 73+/-4%). SNP-induced vascular relaxation showed similar concentration-effect curves in all groups. We conclude that in C57-2K1C mice, the increased reactivity to NE and the decreased endothelium-dependent relaxation contribute to the maintenance of hypertension. The apoE mouse, at early stages of atherosclerosis, shows hyper-reactivity to NE but does not have endothelium dysfunction yet. However, the concurrence of both pathophysiologies does not result in additive effects on the vascular function.
