Decrease in Cochlear Blood Flow with Infusion of Nitric Oxide Synthase Inhibitor and its Recovery with L-arginine Infusion: Comparison with Abdominal Blood Flow and Auricular Blood Flow

Abstract

We observed changes in cochlear blood flow (CoBF), abdominal blood flow (AbBF) and auricular blood flow (AuBF) in rats after administration of the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine-methyl ester (L-NAME). Ten min after i.v. infusion of L-NAME, L-arginine, a substrate of NO, was infused (100 mg/kg) intravenously. Using a laser Doppler flowmeter, changes in blood flow were recorded from the basal turn of the right cochlea, abdominal wall or right auricle, and systemic blood pressure (BP) was recorded simultaneously from the left femoral artery. As another parameter of vascular response, vascular conductance (VC) was calculated from blood flow/mean BP. I.v. infusion of L-NAME produced a dose-dependent depression of cochlear VC at concentrations of 0.2 (-18.9%), 1 (-37.9%), 5 (-45.8%) and 10 mg/kg (-48.3%). Infusion of L-arginine partially reversed the decrease of CoBF caused by L-NAME. The group that received a 0.2 mg/kg infusion of L-NAME showed the largest degree of recovery (23.8%) with L-arginine, while the 10 mg/kg group showed the smallest degree of recovery (10.1%). AbBF also decreased after infusion of L-NAME (5 mg/kg) but to a lesser degree (-41.1% depression of VC) and with no significance compared to the decrease in CoBF (5 mg/kg L-NAME). Likewise, AuBF showed a decrease (-44.0% depression of VC) after infusion of L-NAME (10 mg/kg), the decrease being less than that of CoBF (10 mg/kg L-NAME). Recoveries from these decreased levels of VC in the AbBF and AuBF groups appeared to be smaller than those in the CoBF groups at the same dose of L-NAME (5.5% vs 17.3% in abdominal VC; 5.3% vs 10.1% in auricular VC). In a previous study comparing the CoBF changes caused by i.v. infusion and round window application of L-NAME, we proposed that i.v. infusion of L-NAME in rats primarily affects the precapillary arteriole of the spiral modiolar artery, which effectively regulates cochlear microcirculation as a resistance artery. Thus we assume that there may exist an active pathway of the NO/soluble guanylate cyclase/cyclic guanosine monophosphate system in the above vessels. With regard to the finding of a smaller recovery of VC with L-arginine in both the AbBF and AuBF groups, we consider that differences in L-arginine availability or uptake, and in the synthesis of NO, may exist between the cochlear and cutaneous vasculatures.

Genetics of guanylyl cyclase pathways in the cochlea and their influence on hearing

“…NO also plays a key role in maintaining cochlear blood flow under pathological conditions, such as focal cochlear microcirculation disorder (211). Nonspecific NOS activators increase blood flow in the spiral modiolar artery, and inhibitors decrease it, primarily through actions at the level of the precapillary arteriole (116,117). Opposing actions of nNOS and eNOS have also been shown in the central nervous system, where nNOS is involved in tissue injury, while eNOS maintains blood flow (119).…”