| First Author | Chen L | Year | 2015 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 309 |
| Issue | 5 | Pages | H958-68 |
| PubMed ID | 26209057 | Mgi Jnum | J:226429 |
| Mgi Id | MGI:5697252 | Doi | 10.1152/ajpheart.00430.2015 |
| Citation | Chen L, et al. (2015) Arterial alpha2-Na+ pump expression influences blood pressure: lessons from novel, genetically engineered smooth muscle-specific alpha2 mice. Am J Physiol Heart Circ Physiol 309(5):H958-68 |
| abstractText | Arterial myocytes express alpha1-catalytic subunit isoform Na(+) pumps (75-80% of total), which are ouabain resistant in rodents, and high ouabain affinity alpha2-Na(+) pumps. Mice with globally reduced alpha2-pumps (but not alpha1-pumps), mice with mutant ouabain-resistant alpha2-pumps, and mice with a smooth muscle (SM)-specific alpha2-transgene (alpha2 (SM-Tg)) that induces overexpression all have altered blood pressure (BP) phenotypes. We generated alpha2 (SM-DN) mice with SM-specific alpha2 (not alpha1) reduction (>50%) using nonfunctional dominant negative (DN) alpha2. We compared alpha2 (SM-DN) and alpha2 (SM-Tg) mice to controls to determine how arterial SM alpha2-pumps affect vasoconstriction and BP. alpha2 (SM-DN) mice had elevated basal mean BP (mean BP by telemetry: 117 +/- 4 vs. 106 +/- 1 mmHg, n = 7/7, P < 0.01) and enhanced BP responses to chronic ANG II infusion (240 ng.kg(-1).min(-1)) and high (6%) NaCl. Several arterial Ca(2+) transporters, including Na(+)/Ca(2+) exchanger 1 (NCX1) and sarcoplasmic reticulum and plasma membrane Ca(2+) pumps [sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2) and plasma membrane Ca(2+)-ATPase 1 (PMCA1)], were also reduced (>50%). alpha2 (SM-DN) mouse isolated small arteries had reduced myogenic reactivity, perhaps because of reduced Ca(2+) transporter expression. In contrast, alpha2 (SM-Tg) mouse aortas overexpressed alpha2 (>2-fold), NCX1, SERCA2, and PMCA1 (43). alpha2 (SM-Tg) mice had reduced basal mean BP (104 +/- 1 vs. 109 +/- 2 mmHg, n = 15/9, P < 0.02) and attenuated BP responses to chronic ANG II (300-400 ng.kg(-1).min(-1)) with or without 2% NaCl but normal myogenic reactivity. NCX1 expression was inversely related to basal BP in SM-alpha2 engineered mice but was directly related in SM-NCX1 engineered mice. NCX1, which usually mediates arterial Ca(2+) entry, and alpha2-Na(+) pumps colocalize at plasma membrane-sarcoplasmic reticulum junctions and functionally couple via the local Na(+) gradient to help regulate cell Ca(2+). Altered Ca(2+) transporter expression in SM-alpha2 engineered mice apparently compensates to minimize Ca(2+) overload (alpha2 (SM-DN)) or depletion (alpha2 (SM-Tg)) and attenuate BP changes. In contrast, Ca(2+) transporter upregulation, observed in many rodent hypertension models, should enhance Ca(2+) entry and signaling and contribute significantly to BP elevation. |
