Role of microvascular rarefaction in the increased arterial pressure in mice lacking for the endothelial nitric oxide synthase gene (eNOS3pt−/−)
N Kubis, C Richer, V Domergue… - Journal of …, 2002 - journals.lww.com
N Kubis, C Richer, V Domergue, JF Giudicelli, BI Lévy
Journal of hypertension, 2002•journals.lww.comObjectives Mechanisms involved in hypertension in homozygous mice for the defective
endothelial nitric oxide synthase gene (eNOS−/−) have not been fully elucidated. As NO is a
potent vasodilator agent and possibly promotes angiogenesis, we investigated whether
vasoconstriction and/or microvascular rarefaction could explain hypertension in these mice.
Methods Immunohistochemistry with mouse monoclonal smooth muscle α-actin antibody
was used to detect arterioles, and quantification of arteriolar density was performed in the …
endothelial nitric oxide synthase gene (eNOS−/−) have not been fully elucidated. As NO is a
potent vasodilator agent and possibly promotes angiogenesis, we investigated whether
vasoconstriction and/or microvascular rarefaction could explain hypertension in these mice.
Methods Immunohistochemistry with mouse monoclonal smooth muscle α-actin antibody
was used to detect arterioles, and quantification of arteriolar density was performed in the …
Abstract
Objectives
Mechanisms involved in hypertension in homozygous mice for the defective endothelial nitric oxide synthase gene (eNOS−/−) have not been fully elucidated. As NO is a potent vasodilator agent and possibly promotes angiogenesis, we investigated whether vasoconstriction and/or microvascular rarefaction could explain hypertension in these mice.
Methods
Immunohistochemistry with mouse monoclonal smooth muscle α-actin antibody was used to detect arterioles, and quantification of arteriolar density was performed in the left ventricle and in the gracilis muscle of 12-week-old male eNOS+/+ and eNOS−/− mice. Haemodynamic parameters–mean arterial pressure (MAP), cardiac index (CI), total peripheral résistance (TPR), myocardial blood flow, muscular blood flow and corresponding resistances–were measured or calculated using the fluorescent microsphere method in basal conditions and after infusion of sodium nitroprusside (SNP)(5 to 150 μg/kg per min) in eNOS−/− mice, compared with eNOS+/+ mice.
Results
We evidenced a significant decrease in arteriolar density in the heart (− 16%, P< 0.02) and in the gracilis muscle (− 22%, P< 0.05) in eNOS−/− mice. In basal conditions, eNOS−/− mice developed significant hypertension (MAP= 127±14 versus 77±14 mmHg, P< 0.001) associated with decreased CI (− 29%, P< 0.001) and increased TPR (+ 125%, P< 0.001). Coronary and gracilis muscular resistances were increased (by 75 and 89% respectively, P< 0.001) compared with eNOS+/+ mice, whereas myocardial and skeletal muscle tissue blood flows were not affected. After SNP administration (10 μg/kg per min), a dose that did not significantly modify haemodynamic parameters in eNOS+/+ mice, MAP, TPR and regional resistances were normalized in eNOS−/− mice, showing that vasodilation may correct hypertension in eNOS−/− mice. However, under maximal vasodilating conditions, TPR and regional resistances remained significantly higher in eNOS−/− mice than those of eNOS+/+ mice.
Conclusion
Anatomical and functional results show that both vasoconstriction and arteriolar rarefaction are involved in hypertension of eNOS−/− mice. Indeed, under maximal vasodilation, arterial pressure and TPR remained significantly higher in eNOS−/− mice than in eNOS+/+ mice, evidencing a major role of microvascular rarefaction in this model of hypertension.
Lippincott Williams & Wilkins