| First Author | Zhang J | Year | 2019 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 316 |
| Issue | 2 | Pages | H298-H310 |
| PubMed ID | 30461304 | Mgi Jnum | J:269600 |
| Mgi Id | MGI:6273704 | Doi | 10.1152/ajpheart.00185.2018 |
| Citation | Zhang J, et al. (2019) Na(+)/Ca(2+) exchanger overexpression in smooth muscle augments cytosolic Ca(2+) in femoral arteries of living mice. Am J Physiol Heart Circ Physiol 316(2):H298-H310 |
| abstractText | Plasma membrane Na(+)/Ca(2+) exchanger-1 (NCX1) helps regulate the cytosolic Ca(2+) concentration ([Ca(2+)]CYT) in arterial myocytes. NCX1 mediates both Ca(2+) entry and exit and tends to promote net Ca(2+) entry in partially constricted arteries. Mean blood pressure (telemetry) is elevated by approximately 10 mmHg in transgenic (TG) mice that overexpress NCX1 specifically in smooth muscle. We tested the hypothesis that NCX1 overexpression mediates Ca(2+) gain and elevated [Ca(2+)]CYT in exposed femoral arteries that also express the Ca(2+) biosensor exogenous myosin light chain kinase. [Ca(2+)]CYT and the NCX1-dependent (SEA0400-sensitive) component, approximately 15% of total basal constriction in controls, were increased in TG arteries, but constrictions to phenylephrine and ANG II were comparable in TG and control arteries. Normalized phenylephrine dose-response curves and constriction to 30 and 300 ng/kg iv ANG II were virtually identical in control and TG arteries. ANG II-evoked constrictions, superimposed on elevated basal tone, accounted for the larger blood pressure responses to ANG II in TG arteries. TG and control mouse arteries fit the same pCa-constriction relationship over a wide range of pCa ( approximately 125-500 nM). Vasodilation to acetylcholine, normalized to passive diameter, was also comparable in TG and control arteries, implying normal endothelial function. TG artery Na(+) nitroprusside (nitric oxide donor)-induced dilations were, however, shifted to lower Na(+) nitroprusside concentrations, indicating that TG myocyte vasodilator mechanisms were augmented. Maximum arterial dilation was comparable in TG and control mice, although passive diameter was approximately 6-7% smaller in TG mice. The changes in TG arteries were apparently largely functional rather than structural, despite the congenital hypertension. NEW & NOTEWORTHY Smooth muscle Na(+)/Ca(2+) exchanger-1 transgene overexpression (TG mice) increases femoral artery basal cytosolic Ca(2+) concentration ([Ca(2+)]CYT) and tone in vivo and raises blood pressure. Arterial constriction to phenylephrine and angiotensin II are normal but superimposed on the augmented basal [Ca(2+)]CYT and tone (constriction) in TG mouse arteries. Similar effects in resistance arteries would explain the elevated blood pressure. Acetylcholine-induced vasodilation is unimpaired, implying a normal endothelium, but TG arteries are hypersensitive to sodium nitroprusside. |
