Desensitisation and Calcium-sensitivity in the Isolated Perfused Rat Tail Artery: the Influence of Time and Some Other Factors

ANDREW C. UGWU1, GODFREY L. SMITH, DAVID J. MILLER AND JOHN C. MCGRATH. Autonomic Physiology Unit, Institute of Physiology, University of Glasgow, Glasgow G12 8QQ, Scotland. ____________________________________________________________________________________________________ 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) (3μM) and potassium chloride (KCl) (100mM) were obtained in Ca2+-buffered saline. Activators 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. 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.