Mechanism of Contraction of Rat Isolated Tail Arteries by Hyposmotic Solutions

Abstract

Contraction induced by hyposmotic swelling was examined in rat tail arteries mounted on a myograph containing a modified Krebs physiological saline solution (PSS) containing 50 mM mannitol (300 mosm/l). Hyposmotic swelling was induced by removing mannitol. In arteries having basal tone or arteries precontracted with K⁺ or the thromboxane mimetic U-46619, removal of mannitol caused a concentration dependent contraction of rat tail arteries. Concurrent measurement of tension and intracellular calcium [Ca²⁺]_iin arteries loaded with fura-2 showed that both tension and [Ca²⁺]_i increased on exposure to a hyposmotic solution. Removal of endothelium or inhibition of nitric oxide and cyclooxygenase together did not affect contractile responses. Removal of extracellular Ca²⁺ abolished the contractile response to hyposmotic solution and NiCl₂, a nonspecific inhibitor of Ca²⁺ influx pathways, blocked the rise in [Ca²⁺]_i and tension in response to a hyposmotic solution. Verapamil and nisoldipine, inhibitors of Ca_v1.2 (L-type) calcium channels significantly reduced the contractile response to a hyposmotic solution. Addition of NiCl₂ to nisoldipine caused an additional inhibition of the response to a hyposmotic solution. Inhibition of calcium release from the sarcoplasmic reticulum by ryanodine or cyclopiazonic acid (CPA) did not cause any change in the tension response to a hyposmotic solution. CPA did not significantly inhibit the response to a hyposmotic solution in the presence of N^G-methyl-L-arginine, oxyhaemoglobin and indomethacin. We conclude that contraction induced by a hyposmotic solution is largely due to Ca_v1.2 calcium channels although other Ca²⁺ influx pathways also contribute.

Vascular Smooth Muscle Contraction Evoked by Cell Volume Modulation: Role of the Cytoskeleton Network

“…-free medium were also noted in studies of contractions in swollen rat cerebral and tail arteries [38,39]. Recent investigations have demonstrated that contractions in swollen SMC are mediated by activation of Src nonreceptor tyrosine kinase [40] that might be involved in the augmented permeability of unidentified cation channels and sarcolemmal depolarization [38].…”

Src family tyrosine kinases mediate contraction of rat isolated tail arteries in response to a hyposmotic stimulus

“…In contrast, inhibitors of MEK or PDGFR or EGFR had no effect on hypotonic vasoconstriction. Endothelial factors do not play an important role in mediating contraction induced by hypotonic solution as we have shown previously under identical conditions that removal of the endothelium, or incubation with N G -monomethyl- l -arginine, oxyhaemoglobin and indomethacin did not influence contractile responses to hyposmotic solutions [8].…”

“…Contraction to hyposmotic solution was examined by changing the PSS +M to a mannitol-free solution (PSS -M ). Contractions under isosmotic or hyposmotic conditions were conducted on a background of a small (~10% maximum) tone induced by the thromboxane mimetic, U46619 (100-200 nmol/l) to prevent tachyphylaxis [8]. Peak contraction was measured following exposure to PSS -M .…”

“…L-type calcium channels (Ca V 1.2) play an essential role in vasoconstriction in response to both hyposmotic stimuli [5,6] and increased transmural pressure [7]. We recently showed that rat isolated tail arteries contracted on exposure to a hyposmotic solution, and that this was largely dependent on Ca v 1.2 [8]. The signalling mechanisms contributing to activation of Ca V 1.2 following such stimuli, however, are not clear.…”

Hypertonic and isotonic potassium solutions have different effects on vessel contractility resulting in differences in optimal resting tension in rat aorta

“…For example, hyperosmotic solution induced contractions in rat and guinea-pig aortas [2] and dilation in rat middle cerebral arteries [3] and skeletal muscle arteries [13] . Hyposmotic solution induced contractions in rat tail arteries [14] . For enzymatic action, one study demonstrated that the dihydropyridine-insensitive component of hypertonic K + -induced contraction in Ca 2+ -free medium was sensitive to protein kinase C inhibitors, H7 and calphostin C [2] .…”