Effects of nitric oxide on diaphragmatic muscle endurance and strength in pigs

Abstract

SUMMARYThe aim of the study was to evaluate the effects of nitric oxide (NO) on diaphragmatic fatigue in fifteen anaesthetized, mechanically ventilated pigs, divided into three groups. The animals were pre-treated with indomethacin (3 mg kg-', I.V.) to block the cyclo-oxygenase pathway. To group 1 pigs (n = 6) NG-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-' I.V.) was administered as a bolus to block endogenous NO production, while group 2 pigs (n = 6) were infused with sodium nitroprusside (SNP, 0 023 mg kg-' min-', I.v.), a donor of NO. Group 3 pigs (n = 3) were used as the controls. We evaluated diaphragmatic strength by measuring the transdiaphragmatic pressure (Pdi) generated during bilateral phrenic nerve stimulation at 10, 20, 30 and 50 Hz, 15 V, while the diaphragmatic endurance was assessed by a 30 s stimulation at 10 Hz, 15 V. Diaphragmatic index was assessed as the ratio of peak force between single twitches performed before and after the 30 s stimulation test. We also evaluated mean systemic (MAP) and pulmonary (MPAP) arterial pressures, pulmonary wedge pressure (Pw), systemic (SVR) and pulmonary vascular resistances (PVR) and cardiac output (CO). L-NAME increased MAP, MPAP, Pw, SVR and PVR, but decreased CO. SNP caused a decrease in MAP, MPAP, Pw and SVR, while PVR and CO did not change. The main finding of this study was that diaphragmatic strength was not significantly weakened after L-NAME administration, except at 10 Hz, while it did not change after SNP infusion. However, both L-NAME and SNP caused significant decreases in diaphragmatic endurance capacity. The fatigue appearing after L-NAME is probably correlated with a decline in diaphragmatic blood flow, as evidenced by the increase in SVR and the decrease in CO, and consequently in oxygen supply. In contrast, the decrease in endurance capacity after SNP infusion can be attributed to a direct action of NO on skeletal muscle.

Spreading of fatigue-related effects from active to inactive parts in the medial gastrocnemius muscle of the cat

“…Free-radicals, such as NO and ROS, are produced during muscle contraction and are directly related to fatigue development by effectively modifying the contractile efficiency (Reid et al 1992a, b;Albertini et al 1997;Reid 1998;Mare´chal and Gailly 1999). Inhibition of NO synthase increases force development, whereas NO donors reduce force (Kobzik et al 1994).…”

“…It is possible that a significant increase in intramuscular pressure during tetanic contractions (Ameredes and Provenzano 1997; Degens et al 1998) could also contribute by mechanically squeezing small blood vessels and thus evoking hypoxia. Free radical gases, such as nitric oxide (NO) and reactive oxygen species (ROS) that form during muscle contraction may also be directly related to processes of fatigue development and effectively modify contractile efficiency (Reid et al 1992a, b;Albertini et al 1997;Reid 1998;Mare´chal and Gailly 1999).…”

Muscle-derived ROS and thiol regulation in muscle fatigue

“…Data from intact muscle preparations show that blockade of RNS synthesis lessens fatigue (32,36), promotes fatigue (4,5,16), or has no effect (8). In part, these divergent findings reflect RNS effects on vascular regulation (4, 5).…”

“…NO donors have complex effects on open probability of the sarcoplasmic reticulum (SR) ryanodine-sensitive calcium-release channel (1,41,76,109). NO donors also depress SR calcium-dependent ATPase activity (46), inhibit actin-myosin cross-bridge cycling (92), lessen the activity of cytochrome-c oxidase (21), disrupt calcium regulation (93), depress force (54), diminish mitochondrial oxygen utilization (21), and accelerate fatigue (4,14,122). Similarly, high levels of RNS secondary to inducible NO synthase upregulation cause weakness and dysfunction in inflammatory states (15,37,102).…”

Effects of nitric oxide on the contraction of skeletal muscle

“…In situ blood-perfused muscles. The two phrenic nerves of pigs were maximally tetanized at various frequencies of stimulation (10-50 Hz) below the frequency of tetanic fusion [44]. The force of pig diaphragm was evaluated as the transdiaphragmatic pressure, P dia , equal to the difference between esophageal and gastric pressures, when the diaphragm contracted under maximal stimulation of…”