| Autor: |
Wang Y; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland.; Department of Physical Education, Shaanxi Normal University, Xi'an, Shaanxi, China., Zhang J; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland., Wier WG; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland., Chen L; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland.; Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland., Blaustein MP; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland.; Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland. |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2021 Jan 01; Vol. 320 (1), pp. H221-H237. Date of Electronic Publication: 2020 Oct 30. |
| DOI: |
10.1152/ajpheart.00487.2020 |
| Abstrakt: |
Arterial smooth muscle Na + /Ca 2+ exchanger-1 (SM-NCX1) promotes vasoconstriction or vasodilation by mediating, respectively, Ca 2+ influx or efflux. In vivo, SM-NCX1 mediates net Ca 2+ influx to help maintain myogenic tone (MT) and neuronally activated constriction. SM-NCX1-TG (overexpressing transgenic) mice have increased MT and mean blood pressure (MBP; +13.5 mmHg); SM-NCX1-KO (knockout) mice have reduced MT and MBP (-11.1 mmHg). Endothelium-dependent vasodilation (EDV) is often impaired in hypertension. We tested whether genetically engineered SM-NCX1 expression and consequent BP changes similarly alter EDV. Isolated, pressurized mesenteric resistance arteries with MT from SM-NCX1-TG and conditional SM-NCX1-KO mice, and femoral arteries in vivo from TG mice were studied. Acetylcholine (ACh)-dilated TG arteries with MT slightly more than control or KO arteries, implying that SM-NCX1 overexpression does not impair EDV. In preconstricted KO, but not TG mouse arteries, however, ACh- and bradykinin-triggered vasodilation was markedly attenuated. To circumvent the endothelium, phenylephrine-constricted resistance arteries were tested with Na-nitroprusside [SNP; nitric oxide (NO) donor] and cGMP. This endothelium-independent vasodilation was augmented in TG but attenuated in KO arteries that lack NCX1-mediated Ca 2+ clearance. Baseline cytosolic Ca 2+ ([Ca 2+ ] cyt ) was elevated in TG femoral arteries in vivo, supporting the high BP; furthermore, SNP-triggered [Ca 2+ ] cyt decline and vasodilation were augmented as NO and cGMP promote myocyte polarization thereby enhancing NCX1-mediated Ca 2+ efflux. The TG mouse data indicate that BP elevation does not attenuate endothelium-dependent vasodilation. Thus, in essential hypertension and many models the endothelial impairment that supports the hypertension apparently is not triggered by BP elevation but by extravascular mechanisms. NEW & NOTEWORTHY Endothelium-dependent, ACh-induced vasodilation (EDV) is attenuated, and arterial myocyte Na + /Ca 2+ exchangers (NCX1) are upregulated in many forms of hypertension. Surprisingly, mildly hypertensive smooth muscle-specific (SM)-NCX1 transgenic mice exhibited modestly enhanced EDV and augmented endothelium-independent vasodilation (EIV). Conversely, mildly hypotensive SM-NCX1-knockout mice had greatly attenuated EIV. These adaptations help compensate for NCX1 expression-induced alterations in cytosolic Ca 2+ and blood pressure (BP) and belie the view that elevated BP, itself, causes the endothelial dysregulation in hypertension. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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