期刊
BIOMEDICINES
卷 11, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines11020344
关键词
ouabain; hemodynamic; migraine; cardiovascular function; in vivo; cardiac pacing; total peripheral resistance; Na+; K+-ATPase; alpha(2)-isoform
Heterozygous mice for the migraine-associated mutation (G301R) in the Na+,K+-ATPase alpha(2)-isoform have decreased expression of cardiovascular alpha(2)-isoform and exhibit a pro-contractile vascular phenotype associated with reduced cardiac efficiency. This study aims to assess the functional contribution of the alpha(2)-isoform to in vivo cardiovascular function and showed that the ouabain-induced vascular response was augmented in alpha(+/G301R)(2) mice, leading to suppressed cardiac function.
Heterozygous mice (alpha(+/G301R)(2) mice) for the migraine-associated mutation (G301R) in the Na+,K+-ATPase alpha(2)-isoform have decreased expression of cardiovascular alpha(2)-isoform. The alpha(+/G301R)(2) mice exhibit a pro-contractile vascular phenotype associated with decreased left ventricular ejection fraction. However, the integrated functional cardiovascular consequences of this phenotype remain to be addressed in vivo. We hypothesized that the vascular response to alpha(2)-isoform-specific inhibition of the Na+,K+-ATPase by ouabain is augmented in alpha(+/G301R)(2) mice leading to reduced cardiac efficiency. Thus, we aimed to assess the functional contribution of the alpha(2)-isoform to in vivo cardiovascular function of wild-type (WT) and alpha(+/G301R)(2) mice. Blood pressure, stroke volume, heart rate, total peripheral resistance, arterial dP/dt, and systolic time intervals were assessed in anesthetized WT and alpha(+/G301R)(2) mice. To address rate-dependent cardiac changes, cardiovascular variables were compared before and after intraperitoneal injection of ouabain (1.5 mg/kg) or vehicle during atrial pacing. The alpha(+/G301R)(2) mice showed an enhanced ouabain-induced increase in total peripheral resistance associated with reduced efficiency of systolic development compared to WT. When the hearts were paced, ouabain reduced stroke volume in alpha(+/G301R)(2) mice. In conclusion, the ouabain-induced vascular response was augmented in alpha(+/G301R)(2) mice with consequent suppression of cardiac function.
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