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Barbara Casadei

Publications and source records attributed to Barbara Casadei.

3 recordsLinked to original sources
PubMed2002

Cardiac nitric oxide synthase 1 regulates basal and beta-adrenergic contractility in murine ventricular myocytes.

BACKGROUND: Evidence indicates that myocardial NO production can modulate contractility, but the source of NO remains uncertain. Here, we investigated the role of a type 1 NO synthase isoform (NOS1), which has been recently localized to the cardiac sarcoplasmic reticulum, in the regulation of basal and beta-adrenergic myocardial contraction. METHODS AND RESULTS: Contraction was assessed in left ventricular myocytes isolated from mice with NOS1 gene disruption (NOS1(-/-) mice) and their littermate controls (NOS1(+/+) mice) at 3 stimulation frequencies (1, 3, and 6 Hz) in basal conditions and during beta-adrenergic stimulation with isoproterenol (2 nmol/L). In addition, we examined the effects of acute specific inhibition of NOS1 with vinyl-L-N-5-(1-imino-3-butenyl)-L-ornithine (L-VNIO, 500 micromol/L). NOS1((-/-)) myocytes exhibited greater contraction at all frequencies (percent cell shortening at 6 Hz, 10.7+/-0.92% in NOS1(-/-) myocytes versus 7.21+/-0.8% in NOS1(+/+) myocytes; P<0.05) with a flat frequency-contraction relationship. Time to 50% relaxation was increased in NOS1(-/-) myocytes at all frequencies (at 6 Hz, 26.53+/-1.4 ms in NOS1(-/-) myocytes versus 21.27+/-1.3 ms in NOS1(+/+) myocytes; P<0.05). L-VNIO prolonged time to 50% relaxation at all frequencies (at 6 Hz, 21.28+/-1.7 ms in NOS1(+/+) myocytes versus 26.45+/-1.4 ms in NOS1(+/+)+L-VNIO myocytes; P<0.05) but did not significantly increase basal contraction. However, both NOS1(-/-) myocytes and NOS1(+/+) myocytes treated with L-VNIO showed a greatly enhanced contraction in response to beta-adrenergic stimulation (percent increase in contraction at 6 Hz, 25.2+/-10.8 in NOS1(+/+) myocytes, 68.2+/-11.2 in NOS1(-/-) myocytes, and 65.1+/-13.2 in NOS1(+/+)+L-VNIO myocytes; P<0.05). CONCLUSIONS: NOS1 disruption enhances basal contraction and the inotropic response to beta-adrenergic stimulation in murine ventricular myocytes. These findings indicate that cardiac NOS1-derived NO plays a significant role in the autocrine regulation of myocardial contractility.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Nitric-oxide-mediated regulation of cardiac contractility and stretch responses.

In the heart, nitric oxide (NO) is constitutively produced by the vascular and endocardial endothelium, the cardiomyocytes and the autonomic nerves. Whereas stimulation of NO release from the vascular endothelium has consistently been shown to quicken the onset of left ventricular (LV) relaxation and cause a small reduction in peak contraction, the role of myocardial NO production in regulating cardiac function appears to be more complex and controversial. Some studies have shown that non-isoform-specific inhibition of NO synthesis with L-arginine analogues has no effect on basal contraction in LV myocytes. However, others have demonstrated that stimulation of myocardial NO production can offset the increase in contraction in response to a rise in intracellular Ca(2+). Cardiac NO production is also activated by stretch and under these conditions NO has been shown to facilitate the Frank-Starling response and to contribute to the increase in intracellular Ca(2+) transients that mediates the slow increase in contraction in response to stretch (i.e., the Anrep effect). These findings suggest that NO can mediate diverse and even contrasting actions within the myocardium, a notion that is difficult to reconcile with the early description of NO as a highly reactive and diffusible molecule possessing minimal specificity in its interactions. The purpose of this short review is to revisit some of the 'controversial' aspects of NO-mediated regulation of myocardial function, taking into account our current understanding of how mammalian cells may target and regulate the synthesis of NO in such a way that NO can serve diverse physiological functions.

Animals↗