| First Author | Iwamoto T | Year | 2004 |
| Journal | Nat Med | Volume | 10 |
| Issue | 11 | Pages | 1193-9 |
| PubMed ID | 15475962 | Mgi Jnum | J:94042 |
| Mgi Id | MGI:3510567 | Doi | 10.1038/nm1118 |
| Citation | Iwamoto T, et al. (2004) Salt-sensitive hypertension is triggered by Ca(2+) entry via Na(+)/Ca(2+) exchanger type-1 in vascular smooth muscle. Nat Med 10(11):1193-9 |
| abstractText | Excessive salt intake is a major risk factor for hypertension. Here we identify the role of Na(+)/Ca(2+) exchanger type 1 (NCX1) in salt-sensitive hypertension using SEA0400, a specific inhibitor of Ca(2+) entry through NCX1, and genetically engineered mice. SEA0400 lowers arterial blood pressure in salt-dependent hypertensive rat models, but not in other types of hypertensive rats or in normotensive rats. Infusion of SEA0400 into the femoral artery in salt-dependent hypertensive rats increases arterial blood flow, indicating peripheral vasodilation. SEA0400 reverses ouabain-induced cytosolic Ca(2+) elevation and vasoconstriction in arteries. Furthermore, heterozygous NCX1-deficient mice have low salt sensitivity, whereas transgenic mice that specifically express NCX1.3 in smooth muscle are hypersensitive to salt. SEA0400 lowers the blood pressure in salt-dependent hypertensive mice expressing NCX1.3, but not in SEA0400-insensitive NCX1.3 mutants. These findings indicate that salt-sensitive hypertension is triggered by Ca(2+) entry through NCX1 in arterial smooth muscle and suggest that NCX1 inhibitors might be useful therapeutically. |
