Nitroxyl increases force development in rat cardiac muscle.

Area of Science:

• Cardiovascular Physiology
• Biochemistry

Background:

• Nitroxyl (HNO), a congener of nitric oxide (NO), is known to enhance cardiac contractility.
• This effect is partly attributed to improved calcium (Ca2+) cycling within cardiac cells.

Purpose of the Study:

• To investigate whether HNO influences cardiac function by altering myofilament-calcium interactions.
• To elucidate the specific mechanisms underlying HNO's positive inotropic effects.

Main Methods:

• Experiments utilized intact rat right ventricular trabeculae.
• Intracellular Ca2+ ([Ca2+]i) was measured using fura-2, and force generation was recorded.
• Dose-dependent effects of HNO donors (Angeli's salt) were assessed.
• Ca2+-activated force and actomyosin ATPase activity were analyzed.

Main Results:

• HNO dose-dependently increased both twitch force and [Ca2+]i transients.
• Developed force increased disproportionately more than [Ca2+]i transients, particularly at higher HNO concentrations.
• HNO enhanced maximal Ca2+-activated force (Fmax) without altering the Ca2+ sensitivity of the myofilaments or actomyosin ATPase activity.
• The effects of HNO were redox-sensitive and could be blocked or reversed by thiol reducing agents.
• Nitric oxide (NO) did not replicate these findings.

Conclusions:

• HNO acts as a cardiac Ca2+ sensitizer, augmenting maximal force production.
• This sensitization mechanism is independent of changes in Ca2+ cycling or actomyosin ATPase activity.
• HNO likely modulates myofilament proteins containing reactive thiolate groups.