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African Journal of Biomedical Research
Ibadan Biomedical Communications Group
ISSN: 1119-5096
Vol. 5, No. 1-2, 2002, pp. 33-42
Bioline Code: md02007
Full paper language: English
Document type: Research Article
Document available free of charge

African Journal of Biomedical Research, Vol. 5, No. 1-2, 2002, pp. 33-42

 en CALCIUM-SENSITIVITY OF SMOOTH MUSCLE CONTRACTION IN THE ISOLATED PERFUSED RAT TAIL ARTERY
Andrew C. Ugwu, Godfrey L Smith, David J. Miller and John McGrath

Abstract

Desensitization and the effects of Bay K 8644 and nifedipine on the calcium-sensitivity of smooth muscle contraction were studied in the isolated perfused rat tail artery, employing the activators noradrenaline (NA) (3μM) sand potassium chloride (KC1) (100mM). Experiments were conduced in Ca2+ - buffered saline. Activities were added when {Ca2+} free was low (1μM) and then {Ca2+ }free was increased stepwise to give a Ca2+ concentration\response curve (CRC) There was a progressive rightward shift of the CRCs with time when a series of curves was constructed. The higher the calcium concentration to which the tissue was exposed during activation, the greater was desensitization. The progressive loss in sensitivity could be attenuated by restricting the range of free calcium used for CRCs to between 1μM and 300μM Ca2+. Results were similar whether activation was by NA or high KC1. When the tissues were pre-exposed to NA (3μM) ("Priming") before constructing CRCs, desensitization was produced more quickly and thus sensitivity became more "stable". However, the {Ca2+} during priming and the maximum (Ca2+ ) in a CRC determined the stable level, high {Ca2+} reducing sensitivity. Priming and maximum at 300μM ca2+ was optimal for avoiding progressive desensitization. Bay K 8644 (0.1μM) decreased the sensitivity to Ca2+ but did not alter the rate of desensitization (activated by either NA or KC1). Desensitization complicated demonstration of potentiation by Bay K 8644 in the same tissue. Nifedipine (0.1μM) decreased the sensitivity of Ca2+ at the first CRC but thereafter CRC's were not significantly different from their controls. Only a small degree of inhibition could be seen between consecutive curves when nifedipine was given after drug-free control responses. Thus the rat tail artery exhibits higher sensitivity to Ca2+ on initial contact with activators. The results suggests that desensitization at some stage in excitation-contraction coupling, possibly by Ca2+ overload, occurs when high extracellular {Ca2+} (2.5 or 5mM) is present during activation by NA. This can be prevented by avoiding high. {Ca2+}, thus allowing prolonged reproducibility of high sensitivity to Ca2+ which, is lost.

** Due to technical difficulties, some figures and images associated with this article may not be available. **

Keywords
Ca2+ sensitivity, desensitization, vascular smooth muscle, noradrenaline, nifedipine, Bay K 8644, rat tail artery

 
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