Editing Sulfur dioxide (section)

===Biochemical and biomedical roles===
Sulfur dioxide or its conjugate base bisulfite is produced biologically as an intermediate in both sulfate-reducing organisms and in sulfur-oxidizing bacteria, as well. The role of sulfur dioxide in mammalian biology is not yet well understood.<ref>{{cite journal |last1=Liu |first1=D. |last2=Jin |first2=H. |last3=Tang |first3=C. |last4=Du |first4=J. |title=Sulfur Dioxide: a Novel Gaseous Signal in the Regulation of Cardiovascular Functions |journal=Mini-Reviews in Medicinal Chemistry |year=2010 |volume=10 |issue=11 |pages=1039–1045 |doi=10.2174/1389557511009011039 |pmid=20540708 }}</ref>  Sulfur dioxide blocks nerve signals from the [[pulmonary stretch receptors]] and abolishes the [[Hering–Breuer reflex|Hering–Breuer inflation reflex]].

It is considered that endogenous sulfur dioxide plays a significant physiological role in regulating [[cardiac]] and [[blood vessel]] function, and aberrant or deficient sulfur dioxide metabolism can contribute to several different cardiovascular diseases, such as [[arterial hypertension]], [[atherosclerosis]], [[pulmonary arterial hypertension]], and [[stenocardia]].<ref>{{cite journal |last1=Tian |first1=Hong |title=Advances in the study on endogenous sulfur dioxide in the cardiovascular system |journal=Chinese Medical Journal |date=November 5, 2014 |volume=127 |issue=21 |pages=3803–3807 |doi=10.3760/cma.j.issn.0366-6999.20133031 |pmid=25382339 |s2cid=11924999 |doi-access=free }}</ref>

It was shown that in children with pulmonary arterial hypertension due to congenital heart diseases the level of [[homocysteine]] is higher and the level of endogenous sulfur dioxide is lower than in normal control children. Moreover, these biochemical parameters strongly correlated to the severity of pulmonary arterial hypertension. Authors considered homocysteine to be one of useful biochemical markers of disease severity and sulfur dioxide metabolism to be one of potential therapeutic targets in those patients.<ref>{{cite journal|vauthors=Yang R, Yang Y, Dong X, Wu X, Wei Y |title=Correlation between endogenous sulfur dioxide and homocysteine in children with pulmonary arterial hypertension associated with congenital heart disease|language=zh|journal=Zhonghua Er Ke Za Zhi|date=Aug 2014|volume=52|issue=8|pages=625–629|pmid=25224243}}</ref>

Endogenous sulfur dioxide also has been shown to lower the [[Cell proliferation|proliferation]] rate of endothelial [[smooth muscle]] cells in blood vessels, via lowering the [[MAPK]] activity and activating [[adenylyl cyclase]] and [[protein kinase A]].<ref>{{cite journal|vauthors=Liu D, Huang Y, Bu D, Liu AD, Holmberg L, Jia Y, Tang C, Du J, Jin H |title=Sulfur dioxide inhibits vascular smooth muscle cell proliferation via suppressing the Erk/MAP kinase pathway mediated by cAMP/PKA signaling|journal=Cell Death Dis.|date=May 2014|volume=5|issue=5|pages=e1251|doi=10.1038/cddis.2014.229|pmid=24853429|pmc=4047873}}</ref> Smooth muscle cell proliferation is one of important mechanisms of hypertensive remodeling of blood vessels and their [[stenosis]], so it is an important pathogenetic mechanism in arterial hypertension and atherosclerosis.

Endogenous sulfur dioxide in low concentrations causes endothelium-dependent [[vasodilation]]. In higher concentrations it causes endothelium-independent vasodilation and has a negative inotropic effect on cardiac output function, thus effectively lowering blood pressure and myocardial oxygen consumption. The vasodilating and bronchodilating effects of sulfur dioxide are mediated via ATP-dependent [[calcium channel]]s and L-type ("dihydropyridine") calcium channels. Endogenous sulfur dioxide is also a potent antiinflammatory, antioxidant and cytoprotective agent. It lowers blood pressure and slows hypertensive remodeling of blood vessels, especially thickening of their intima. It also regulates lipid metabolism.<ref>{{cite journal|vauthors=Wang XB, Jin HF, Tang CS, Du JB |title=The biological effect of endogenous sulfur dioxide in the cardiovascular system.|journal=Eur J Pharmacol|date=November 16, 2011|volume=670|issue=1|doi=10.1016/j.ejphar.2011.08.031|pmid=21925165|pages=1–6}}</ref>

Endogenous sulfur dioxide also diminishes myocardial damage, caused by [[isoproterenol]] [[adrenergic]] hyperstimulation, and strengthens the myocardial antioxidant defense reserve.<ref>{{cite journal|vauthors=Liang Y, Liu D, Ochs T, Tang C, Chen S, Zhang S, Geng B, Jin H, Du J |title=Endogenous sulfur dioxide protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats.|journal=Lab. Invest.|date=Jan 2011|volume=91|issue=1|pages=12–23|doi=10.1038/labinvest.2010.156|pmid=20733562|doi-access=free}}</ref>