K+ Potentiates Hyperosmolarity-induced Vasorelaxations in Rat Skeletal Muscle Arterioles

Overview

Journal Eur J Appl Physiol

Specialty Physiology

Date 2006 Jan 18

PMID 16416320

Authors

Ine De Clerck

Jean-Louis Pannier

Johan Van de Voorde

Affiliations

Soon will be listed here.

Abstract

Several regulatory mechanisms have been proposed for the exercise hyperemia in skeletal muscles. Since different vasoactive factors might interact during the hyperemic response, we investigated the influence of elevated K(+) concentrations on hyperosmolarity (HO)-induced vasorelaxations. Small gluteal rat arteries were isolated and mounted in an organ bath for isometric tension recording. After precontraction with norepinephrine, 20 (S20), 40 (S40) or 60 mM (S60) sucrose was added in control conditions (5 mM K(+); K5) or in the presence of additional 3 (K8) or 5 mM (K10) K(+). Removal of the endothelium and the addition of ouabain, Ba(2+), iberiotoxin or 18-alpha glycyrrhetinic acid (alphaGA) were used to study the underlying mechanisms. Sucrose evoked significant concentration-dependent vasorelaxations (S20 15.62+/-1.61%; S40 26.47+/-1.71%; S60 43.66+/-2.50%), which were significantly increased on addition of 3 and 5 mM. After removal of the endothelium and in the presence of 5 x 10(-5) M alphaGA, the influence of K(+) was significantly blocked but not in the presence of 5 x 10(-5) M ouabain. The K(IR) channel inhibitor Ba(2+) and BK(Ca) channel inhibitor iberiotoxin totally abolished the potentiating effect. We conclude that K(+) significantly enhances the relaxing effect of HO in gluteal blood vessels. We hypothesize that K(+) may stimulate the endothelial K(IR) channels which elicits the release of a mediator of the BK(Ca) channels. This factor may be transferred through myo-endothelial gap-junctions to the smooth muscle cells where modulation of the BK(Ca) channels sensitizes the arteries for hyperosmolarity-induced relaxations.

References

Taylor H, Chaytor A, Evans W, Griffith T . Inhibition of the gap junctional component of endothelium-dependent relaxations in rabbit iliac artery by 18-alpha glycyrrhetinic acid. Br J Pharmacol. 1998; 125(1):1-3. PMC: 1565609. DOI: 10.1038/sj.bjp.0702078. View

SKINNER Jr N, Costin J . Interactions between oxygen, potassium, and osmolality in regulation of skeletal muscle blood flow. Circ Res. 1971; 28:Suppl 1:73-85. View

De Clerck I, Boussery K, Pannier J, Van de Voorde J . Potassium potently relaxes small rat skeletal muscle arteries. Med Sci Sports Exerc. 2003; 35(12):2005-12. DOI: 10.1249/01.MSS.0000099101.39139.FA. View

SKINNER Jr N, Costin J . Interactions of vasoactive substances in exercise hyperemia: O2, K+, and osmolality. Am J Physiol. 1970; 219(5):1386-92. DOI: 10.1152/ajplegacy.1970.219.5.1386. View

Weiger T, Hermann A, Levitan I . Modulation of calcium-activated potassium channels. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2002; 188(2):79-87. DOI: 10.1007/s00359-002-0281-2. View

Mulvany M, Warshaw D . The active tension-length curve of vascular smooth muscle related to its cellular components. J Gen Physiol. 1979; 74(1):85-104. PMC: 2228486. DOI: 10.1085/jgp.74.1.85. View

Triggle C, Ding H . Endothelium-derived hyperpolarizing factor: is there a novel chemical mediator?. Clin Exp Pharmacol Physiol. 2002; 29(3):153-60. DOI: 10.1046/j.1440-1681.2002.03632.x. View

De Clerck I, Guyssens B, Pannier J, Van de Voorde J . Hyperosmolarity causes BK Ca-dependent vasodilatations in rat skeletal muscle arteries. Med Sci Sports Exerc. 2005; 37(10):1697-703. DOI: 10.1249/01.mss.0000176446.13607.b0. View

Calderone V . Large-conductance, ca(2+)-activated k(+) channels: function, pharmacology and drugs. Curr Med Chem. 2002; 9(14):1385-95. DOI: 10.2174/0929867023369871. View

10.

Radegran G, Hellsten Y . Adenosine and nitric oxide in exercise-induced human skeletal muscle vasodilatation. Acta Physiol Scand. 2000; 168(4):575-91. DOI: 10.1046/j.1365-201x.2000.00705.x. View

11.

Scott J, Frohlich E, Hardin R, Haddy F . Na, K, Ca, and Mg ion action on coronary vascular resistance in the dog heart. Am J Physiol. 1961; 201:1095-100. DOI: 10.1152/ajplegacy.1961.201.6.1095. View

12.

Wilson J, Kapoor S, Krishna G . Contribution of potassium to exercise-induced vasodilation in humans. J Appl Physiol (1985). 1994; 77(6):2552-7. DOI: 10.1152/jappl.1994.77.6.2552. View

13.

Shimokawa H, Matoba T . Hydrogen peroxide as an endothelium-derived hyperpolarizing factor. Pharmacol Res. 2004; 49(6):543-9. DOI: 10.1016/j.phrs.2003.10.016. View

14.

Mellander S, Johansson B, Gray S, Jonsson O, Lundvall J, LJUNG B . The effect of hyperosmolarity on intacet and isolated vascular smooth muscle. Possible role in exercise hyperemia. Angiologica. 1967; 4(6):310-22. DOI: 10.1159/000157715. View

15.

DOUGHTY J, Boyle J, Langton P . Blockade of chloride channels reveals relaxations of rat small mesenteric arteries to raised potassium. Br J Pharmacol. 2001; 132(1):293-301. PMC: 1572528. DOI: 10.1038/sj.bjp.0703769. View

16.

Rummery N, Hill C . Vascular gap junctions and implications for hypertension. Clin Exp Pharmacol Physiol. 2004; 31(10):659-67. DOI: 10.1111/j.1440-1681.2004.04071.x. View

17.

Edwards G, Weston A . Potassium and potassium clouds in endothelium-dependent hyperpolarizations. Pharmacol Res. 2004; 49(6):535-41. DOI: 10.1016/j.phrs.2003.11.013. View

18.

Kjellmer I . THE POTASSIUM ION AS A VASODILATOR DURING MUSCULAR EXERCISE. Acta Physiol Scand. 1965; 63:460-8. DOI: 10.1111/j.1748-1716.1965.tb04089.x. View

19.

Massett M, Koller A, Kaley G . Hyperosmolality dilates rat skeletal muscle arterioles: role of endothelial K(ATP) channels and daily exercise. J Appl Physiol (1985). 2000; 89(6):2227-34. DOI: 10.1152/jappl.2000.89.6.2227. View

20.

De Clerck I, Boussery K, Pannier J, Van de Voorde J . Hyperosmolarity increases K+-induced vasodilations in rat skeletal muscle arterioles. Med Sci Sports Exerc. 2005; 37(2):220-6. DOI: 10.1249/01.mss.0000152703.49505.57. View