CALCIUM-CONTRACTION RELATIONSHIP IN RAT MESENTERIC ARTERIAL SMOOTH-MUSCLE - EFFECTS OF EXOGENOUS AND NEUROGENIC NORADRENALINE

We evaluated the relationship between intracellular calcium concentrat ion ([Ca2+](i)) and vasoconstriction during the presence of exogenous noradrenaline (NA) and sympathetic nerve stimulation. An imaging techn ique was used to determine calcium/tension relationships in isolated r at mesenteric resistance arteries that had been mounted for recording of isometric tension development and loaded with Fura-2/AM. Experiment s were performed after depletion of vasodilator neuropeptides and in t he continuous presence of 1 mu M propanolol. 3 mu M indomethacin, and 30 mu M nitro-L-arginine. NA (10 mu M) was shown first to induce a fur ther increase in tension, but not [Ca2+](i), during the contraction in duced by 125 mM K+. Subsequently, calcium/tension relationships were d etermined during stimulation with graded increases in extracellular [K +] (5.9-125 mM K+), cumulative administration of NA (0.2-10 mu M) and electrical field stimulation of perivascular nerves (EFS, 1-16 Hz). A basal calcium/tension relationship without the calcium-sensitizing pro perty of NA was constructed using a cumulative concentration/response curve of 5.9-125 mM K+ in arteries after prior exposure to the irrever sible alpha-adrenoceptor antagonist phenoxybenzamine (POB). K+ series before and during alpha-blockade were also studied using the combinati on of the alpha(1)-antagonist prazosin and alpha(2)-antagonist yohimbi ne yielding comparable results as with POB. Calcium/tension curves obt ained in the presence of NA, K+ and during EFS all were shifted to the left compared with the basal condition and all showed a similar slope indicating that neurogenically released NA is equally capable of indu cing calcium sensitization in smooth muscle of mesenteric resistance a rteries as exogenously applied NA. In the presence of exogenous and en dogenous NA we not only observed an elevated contractile response for a given increase in [Ca2+](i), but also an attenuated rise in [Ca2+](i ) for a given intensity of stimulation. This suggests that the agonist -induced calcium sensitization is accompanied by a reduction of the ri se in [Ca2+](i).