title: Nitric Oxide and cGMP in Regulation of Arterial Tone.
abstract: Nitric Oxide (NO) is an important factor in the control of vascular tone and peripheral resistance. Guanosine 3',5'-monophosphate (cGMP) mediates NO-induced vasorelaxation via multiple mechanisms, including decreased Ca(2+) entry and release, enhanced Ca(2+) extrusion, and inhibition of sensitization of myofilaments to Ca(2+) caused by some agonists such as norepinephrine (but not others such as ATP). This may result in differential effects of NO, depending on the agonist and the smooth muscle phenotype. In blood vessels exposed to inflammatory stimuli (for instance in endotoxemia), enhanced NO production causes loss of vascular reactivity to vasoconstrictor agents. This results from the induction of NO synthase activity in vascular cells, especially in the adventitia. The role of the adventitia may explain differences between large and small resistance arteries, in addition to the phenotype of smooth muscle cells. Protein-bound dinitrosyl non-heme iron complexes with thiols can be generated in arteries subsequent to the induction of NO synthase. Low molecular thiols can displace Fe-NO from these complexes, leading to activation of guanylyl cyclase and vasorelaxation. This may represent a novel mechanism of NO storage and release, enabling prolonged effects of NO in blood vessels and, perhaps, protection of vascular tissue against oxidative injury in sepsis and other inflammatory diseases.
authors.affiliation: Laboratoire de Pharmacologie et Physiopathologie Cellulaires, ERS CNRS 653, Université Louis Pasteur de Strasbourg, Illkirch, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Stoclet
authors.forename: R
authors.initials: R
authors.lastname: Andriantsitohaina
authors.forename: A
authors.initials: A
authors.lastname: Kleschyov
authors.forename: B
authors.initials: B
authors.lastname: Muller