| Autor: |
Lorenz, John N., Loreaux, Elizabeth L., Dostanic-Larson, Iva, Lasko, Valerie, Schnetzer, J. Renee, Paul, Richard J., Lingrel, Jerry B. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Jul2008, Vol. 295 Issue 1, pH273-H280, 7p, 9 Graphs |
| Abstrakt: |
ACTH-induced-hypertension is commonly employed as a model of stress-related hypertension, and despite extensive investigation, the mechanisms underlying elevated blood pressure (BP) are not well understood. We have reported that ACTH treatment increases tail-cuff systolic pressure in wild-type mice but not in mutant mice expressing ouabain-resistant α2-Na+-K+-ATPase subunits (α2RR mice). Since tail-cuff measurements involve restraint stress, the present study used telemetry to distinguish between an effect of ACTH on resting BP vs. an ACTH-enhanced stress response. We also sought to explore the mechanisms underlying ACTH-induced BP changes in mutant α2RR mice vs. wild-type mice (ouabain-sensitive α2-Na+-K+-ATPase. α2S/S mice). Baseline BP was not different between the two genotypes, but after 5 days of ACTH treatment, BP increased in α2S/S (104.0 ± 2.6 to 117.7 ± 3.0 mmHg) but not in α2RR mice (108.2 ± 3.2 to 111.5 ± 4.0 mmHg). To test the hypothesis that ACTH hypertension is related to inhibition of α2-Na+-K+-ATPase on vascular smooth muscle by endogenous cardiotonic steroids, we measured BP and regional blood flow. Results suggest a differential sensitivity of renal, mesenteric, and cerebral circulations to ACTH and that the response depends on the ouabain sensitivity of the α2-Na+-K+-ATPase. Baseline cardiac performance was elevated in α2S/S but not α2RR mice. Overall, the data establish that the α2-Na+- K+-ATPase ouabain-binding site is of central importance in the development of ACTH-induced hypertension. The mechanism appears to be related to alterations in cardiac performance, and perhaps vascular tone in specific circulations, presumably caused by elevated levels of circulating cardiotonic steroids. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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