Faculty Collaboration Database

NOS inhibition enhances myogenic tone by increasing rho-kinase mediated Ca2+ sensitivity in the male but not the female gerbil spiral modiolar artery. PLoS One 2013;8(1):e53655

Date

01/10/2013

Pubmed ID

23301097

Pubmed Central ID

PMC3536759

DOI

10.1371/journal.pone.0053655

Scopus ID

2-s2.0-84871898322 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

Cochlear blood flow regulation is important to prevent hearing loss caused by ischemia and oxidative stress. Cochlear blood supply is provided by the spiral modiolar artery (SMA). The myogenic tone of the SMA is enhanced by the nitric oxide synthase (NOS) blocker L-N(G)-nitro-arginine (LNNA) in males, but not in females. Here, we investigated whether this gender difference is based on differences in the cytosolic Ca(2+) concentration and/or the Ca(2+) sensitivity of the myofilaments. Vascular diameter, myogenic tone, cytosolic Ca(2+), and Ca(2+) sensitivity were evaluated in pressurized SMA segments isolated from male and female gerbils using laser-scanning microscopy and microfluorometry. The gender difference of the LNNA-induced tone was compared, in the same vessel segments, to tone induced by 150 mM K(+) and endothelin-1, neither of which showed an apparent gender-difference. Interestingly, LNNA-induced tone in male SMAs was observed in protocols that included changes in intramural pressure, but not when the intramural pressure was held constant. LNNA in male SMAs did not increase the global Ca(2+) concentration in smooth muscle cells but increased the Ca(2+) sensitivity. This increase in the Ca(2+) sensitivity was abolished in the presence of the guanylyl cyclase inhibitor ODQ or by extrinsic application of either the nitric oxide (NO)-donor DEA-NONOate or the cGMP analog 8-pCPT-cGMP. The rho-kinase blocker Y27632 decreased the basal Ca(2+) sensitivity and abolished the LNNA-induced increase in Ca(2+) sensitivity in male SMAs. Neither LNNA nor Y27632 changed the Ca(2+) sensitivity in female SMAs. The data suggest that the gender difference in LNNA-induced tone is based on a gender difference in the regulation of rho-kinase mediated Ca(2+) sensitivity. Rho-kinase and NO thus emerge as critical factors in the regulation of cochlear blood flow. The larger role of NO-dependent mechanisms in male SMAs predicts greater restrictions on cochlear blood flow under conditions of impaired endothelial cell function.

Author List

Reimann K, Krishnamoorthy G, Wangemann P

Author

Gayathri K. Natarajan Research Scientist I in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arteries
Calcium
Cytophotometry
Cytosol
Female
Gerbillinae
Male
Microscopy, Confocal
Muscle Contraction
Muscle Development
Muscles
Nitric Oxide Synthase
Nitroarginine
Pressure
Sex Factors
rho-Associated Kinases