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African Journal of Biomedical Research
Ibadan Biomedical Communications Group
ISSN: 1119-5096
Vol. 3, No. 3, 2000, pp. 153-159
Bioline Code: md00045
Full paper language: English
Document type: Research Article
Document available free of charge

African Journal of Biomedical Research, Vol. 3, No. 3, 2000, pp. 153-159

 en DESENSITISATION AND CALCIUM-SENSITIVITY IN THE ISOLATED PERFUSED RAT TAIL ARTERY: THE INFLUENCE OF TIME AND SOME OTHER FACTORS
ANDREW C. UGWU, GODFREY L. SMITH, DAVID J. MILLER AND JOHN C. MCGRATH

Abstract

The calcium sensitivity of vascular smooth muscle contraction and experimentally-induced desensitisation to noradrenaline were studied in the isolated perfused rat tail artery. Responses to the activators noradrenaline (NA) (3mM) and potassium chloride (KCl) (100mM) were obtained in Ca2+-buffered saline. Activators were added when [Ca2+] free was low (1mM) 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. Desensitisation was not a function of time elapsed before first testing and could be reduced by increasing the interval between CRCs, reducing [NA] or doubling [glucose]. Thus the rat tail artery exhibits higher sensitivity to Ca2+ on initial contact with activators. The results suggest that desensitisation 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 allowing recovery through leaving longer intervals between CRCs, thus allowing prolonged reproducibility of high sensitivity to Ca2+ which, otherwise, is lost. Desensitisation was essentially similar whether activation was by NA, 5HT or high [KCl]. NA caused desensitisation to 5HT more effectively than 5HT caused desensitisation to NA. The results are discussed in relation to the experimental conditions necessary to examine the sensitivity of vascular smooth muscle contraction to extracellular calcium and noradrenaline and to the mechanisms which may underline rapid desensitisation.

Keywords
Ca2+ sensitivity, desensitisation, smooth muscle, noradrenaline, 5-hydroxytryptamine, rat tail artery

 
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