A number of studies have recently reinvestigated the rapid hyperaemia that occurs in response to a brief muscle contraction and to external compression of the muscle (Clifford & Tschakovsky, 2008). Both stimuli have been suggested to produce a rapid dilatation, induced by the transmural pressure changes in the vascular network. Several types of mechano-sensitive ion channels (MSC) in smooth muscle and/or endothelium are potentially involved. Gadolinium (Gd3+) is considered to be one among the most effective MSC blockers (Schubert & Mulvany, 1999). It was reported to effectively reduce the myogenic response to sustained transmural pressure changes in isolated vessels but its effectiveness in vivo has been poorly investigated. Aim of the present study is to investigate in vivo the effect of local administration of Gd3+ on basal blood flow and on the rapid hyperaemia produced by external muscle compression. The adopted model allows for continuous monitoring of blood flow in the purely muscular masseteric artery. The study complies with the national guidelines for animal care Eight rabbits were anesthetized with i.v. administration of urethane (400 mg/kg), ketamine and xylazine (initial dose of 5 and 1.5 mg/kg, respectively, then continuously infused as needed). Hyperemic responses were induced by 1-s lasting compression of the masseter muscle by means of a cylindrical head (diameter: 2 cm) moved by a computer-driven motor. Hyperemic responses were repeatedly evoked before and 15, 30 and 45 min after close arterial injection of Gd3+, administered at progressive concentrations of 0.1, 1 and 10 mM. Each dose was infused in 2 min and after 1-h interval from previous administration. Injection rate was set to 50% of measured blood flow in the masseteric artery resulting in approximate plasma concentrations of 0.045, 0.45 and 4.5 mM. Both basal blood flow and the amplitude of the hyperaemic response were significantly dependent on Gd3+ concentration (p<0.05) but not on time (2-ways ANOVA). With respect to the control (pre-Gd3+) condition the following changes were observed in basal blood flow at the different plasma concentrations: +11 ± 25% at 0.045 mM (p=0.90), +69 ± 71% at 0.45 mM (p<0.05) and -54 ± 35% at 4.5 mM (p<0.05) and in the amplitude of the hyperaemic response: -12 ± 4% at 0.045 mM (p=0.24), -26 ± 26% at 0.45 mM (p<0.05) and -94 ±4% at 4.5 mM (p<0.05 While at the highest concentration the observed effects could be secondary to the low solubility of Gd3+, at lower concentrations Gd3+ significantly increased basal muscle blood flow and decreased the rapid hyperaemic response to muscle compression. This supports the notion that MSCs are implicated in the maintenance of basal myogenic tone and that they have a role in the rapid dilatation induced by muscle compression.