Helen E. Collins Laboratory

Investigating Mechanisms Underlying Female Cardiovascular Resilience and Health

Inotropic Response of Cardiac Ventricular Myocytes to beta-Adrenergic Stimulation With Isoproterenol Exhibits Diurnal Variation: Involvement of Nitric Oxide


Journal article


Helen E Collins, Glenn C. Rodrigo
Circulation research, 2010

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APA   Click to copy
Collins, H. E., & Rodrigo, G. C. (2010). Inotropic Response of Cardiac Ventricular Myocytes to beta-Adrenergic Stimulation With Isoproterenol Exhibits Diurnal Variation: Involvement of Nitric Oxide. Circulation Research.


Chicago/Turabian   Click to copy
Collins, Helen E, and Glenn C. Rodrigo. “Inotropic Response of Cardiac Ventricular Myocytes to Beta-Adrenergic Stimulation With Isoproterenol Exhibits Diurnal Variation: Involvement of Nitric Oxide.” Circulation research (2010).


MLA   Click to copy
Collins, Helen E., and Glenn C. Rodrigo. “Inotropic Response of Cardiac Ventricular Myocytes to Beta-Adrenergic Stimulation With Isoproterenol Exhibits Diurnal Variation: Involvement of Nitric Oxide.” Circulation Research, 2010.


BibTeX   Click to copy

@article{helen2010a,
  title = {Inotropic Response of Cardiac Ventricular Myocytes to beta-Adrenergic Stimulation With Isoproterenol Exhibits Diurnal Variation: Involvement of Nitric Oxide},
  year = {2010},
  journal = {Circulation research},
  author = {Collins, Helen E and Rodrigo, Glenn C.}
}

Abstract

Rationale: Although >10% of cardiac gene expression displays diurnal variations, little is known of their impact on excitation–contraction coupling. Objective: To determine whether the time of day affects excitation–contraction coupling in rat ventricles. Methods and Results: Left ventricular myocytes were isolated from rat hearts at 2 opposing time points, corresponding to the animals resting or active periods. Basal contraction and [Ca2+]i was significantly greater in myocytes isolated during the resting versus active periods (cell shortening 12.4±0.3 versus 11.0±0.2%; P<0.05 and systolic [Ca2+]i 422±12 versus 341±9 nmol/L; P<0.01. This corresponded to a greater sarcoplasmic reticulum (SR) Ca2+ load (672±20 versus 551±13 nmol/L P<0.001). The increase in systolic [Ca2+]i in response to isoproterenol (>3 nmol/L) was also significantly greater in resting versus active period myocytes, reflecting a greater SR Ca2+ load at this time. This diurnal variation in response of Ca2+-homeostasis to isoproterenol translated to a greater incidence of arrhythmic activity in resting period myocytes. Inhibition of neuronal NO synthase during stimulation with isoproterenol, further increased systolic [Ca2+]i and the percentage of arrhythmic myocytes, but this effect was significantly greater in active period versus resting period myocytes. Quantitative RT-PCR analysis revealed a 2.65-fold increase in neuronal NO synthase mRNA levels in active over resting period myocytes (P<0.05). Conclusions: The threshold for the development of arrhythmic activity in response to isoproterenol is higher during the active period of the rat. We suggest this reflects a reduction in SR Ca2+ loading and a diurnal variation in neuronal NO synthase signaling.


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