| First Author | Kubis N | Year | 2002 |
| Journal | J Hypertens | Volume | 20 |
| Issue | 8 | Pages | 1581-7 |
| PubMed ID | 12172320 | Mgi Jnum | J:106000 |
| Mgi Id | MGI:3617118 | Doi | 10.1097/00004872-200208000-00021 |
| Citation | Kubis N, et al. (2002) Role of microvascular rarefaction in the increased arterial pressure in mice lacking for the endothelial nitric oxide synthase gene (eNOS3pt-/- ). J Hypertens 20(8):1581-7 |
| abstractText | 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 alpha-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 resistance (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 microg/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 microg/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. |
