A theoretical model of nitric oxide transport in arterioles: frequency- vs. amplitude-dependent control of cGMP formation.
Nitric oxide (NO) plays many important physiological roles, including the regulation of vascular smooth muscle tone. In response to hemodynamic or agonist stimuli, endothelial cells produce NO, which can diffuse to smooth muscle where it activates soluble guanylate cyclase (sGC), leading to cGMP formation and smooth muscle relaxation. The close proximity of red blood cells suggests, however, that a significant amount of NO released will be scavenged by blood, and thus the issue of bioavailability of endothelium-derived NO to smooth muscle has been investigated experimentally and theoretically. We formulated a mathematical model for NO transport in an arteriole to test the hypothesis that transient, burst-like NO production can facilitate efficient NO delivery to smooth muscle and reduce NO scavenging by blood. The model simulations predict that 1) the endothelium can maintain a physiologically significant amount of NO in smooth muscle despite the presence of NO scavengers such as hemoglobin and myoglobin; 2) under certain conditions, transient NO release presents a more efficient way for activating sGC and it can increase cGMP formation severalfold; and 3) frequency-rather than amplitude-dependent control of cGMP formation is possible. This suggests that it is the frequency of NO bursts and perhaps the frequency of Ca(2+) oscillations in endothelial cells that may limit cGMP formation and regulate vascular tone. The proposed hypothesis suggests a new functional role for Ca(2+) oscillations in endothelial cells. Further experimentation is needed to test whether and under what conditions in silico predictions occur in vivo.
Dept. of Biomedical Engineering, Johns Hopkins Univ. School of Medicine, 613 Traylor Bldg., 720 Rutland Ave., Baltimore, MD 21205, USA. tsoukias@bme.jhu.edu
Nikolaos M
NM
Tsoukias
Mahendra
M
Kavdia
Aleksander S
AS
Popel
D001160:Arterioles / Q000502:physiology*; D001803:Blood Transfusion; D020013:Calcium Signaling / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism*; D004058:Diffusion; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*
D009569:Nitric Oxide; D006152:Cyclic GMP