Editing Vasoconstriction (section)

==General mechanism==
The mechanism that leads to vasoconstriction results from the increased concentration of [[calcium]] (Ca<sup>2+</sup> [[ions]]) within vascular [[smooth muscle cells]].<ref>
{{cite journal
| author1=Michael P. Walsh
| author2=David P. Wilson
| author3=Marija Susnjar
| author4=Enikő Kiss
| author5=Cindy Sutherland
| display-authors=1
| date=2005-08-01<!--Print date and PubMed Central date-->
| orig-date=Published on Journal website 2005-07-26
| title=Thromboxane A<sub>2</sub>-induced contraction of rat caudal arterial smooth muscle involves activation of Ca<sup>2+</sup> entry and Ca<sup>2+</sup>sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697
| journal=Biochem J
| volume=389
| issue=3
| pages=763–774
| doi=10.1042/BJ20050237
| pmc=1180727
| pmid=15823093
| language=en
| quote=These results suggest that U-46619 elicits contraction of rat caudal arterial smooth muscle by activating Ca<sup>2+</sup> entry from the extracellular space, which may or may not involve Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release from the SR (sarcoplasmic reticulum). ... A key step in the contractile response to U-46619 appears to be the entry of extracellular Ca<sup>2+</sup>, since it was abolished by removal of extracellular Ca<sup>2+</sup> (Figure 2A). ... In the rat caudal artery, U-46619-mediated contractile responses have an absolute requirement for Ca<sup>2+</sup>, which enters from the extracellular pool, is independent of intracellular Ca<sup>2+</sup> stores and is blocked by ROK inhibition.
}}
</ref> However, the specific mechanisms for generating an increased intracellular concentration of calcium depends on the vasoconstrictor. Smooth muscle cells are capable of generating [[action potentials]], but this mechanism is rarely utilized for contraction in the vasculature. [[Hormonal]] or pharmacokinetic components are more physiologically relevant. Two common stimuli for eliciting smooth muscle contraction are circulating [[epinephrine]] and activation of the [[sympathetic nervous system]] (through release of [[norepinephrine]]) that directly innervates the muscle. These compounds interact with cell surface [[adrenergic receptors]]. Such stimuli result in a [[signal transduction]] cascade that leads to increased intracellular calcium from the [[sarcoplasmic reticulum]] through [[Inositol triphosphate|IP3]]-mediated calcium release, as well as enhanced calcium entry across the [[sarcolemma]] through [[calcium channels]]. The rise in intracellular calcium complexes with [[calmodulin]], which in turn activates [[myosin light-chain kinase]]. This enzyme is responsible for [[phosphorylation|phosphorylating]] the light chain of [[myosin]] to stimulate cross-bridge cycling.<ref>{{cite journal |title=Control of cross-bridge cycling by myosin light chain phosphorylation in mammalian smooth muscle |journal=Acta Physiologica Scandinavica |date=December 1998 |volume=164 |issue=4 |pages=389–400 |doi=10.1046/j.1365-201x.1998.00450.x |pmid=9887963 |last1=Butler |last2=Siegman }}</ref>

Once elevated, the intracellular calcium concentration is returned to its normal concentration through a variety of protein pumps and calcium exchangers located on the plasma membrane and sarcoplasmic reticulum. This reduction in calcium removes the stimulus necessary for contraction, allowing for a return to baseline.{{citation needed|date=April 2022}}