THE EFFECTS OF EXTRACELLULAR PH AND CALCIUM CHANGE ON FORCE AND INTRACELLULAR CALCIUM IN RAT VASCULAR SMOOTH-MUSCLE

1. In order to investigate the mechanism whereby changes in external pH (pH(o)) alter tone in rat mesenteric resistance vessels, we have made simultaneous measurements of tension and intracellular Ca2+ [Ca2+](i). Strips of mesenteric artery were loaded with the Ca2+-sensitive indicator indo-1 and superfused with physiological salt solution at pH 7.4 and 37 degrees C. 2. An increase of pH(o) from 7.4 to 7.9 produced an increase in tension. This was accompanied by an increase in [Ca2+](i) in resting and high-K+-depolarized vessels. Acidification to 6.9 reduced tension and was associated with a fall in [Ca2+](i). Over the pH(i) range examined, 6.6-7.9, parallel changes in [Ca2+](i) and tension were found in K+-activated vessels. 3. In contrast to the relatively slow change in [Ca2+](i), pH(i) and tension with change of pH(o), depolarization produced rapid changes in [Ca2+](i) and tension, consistent with a more direct action on Ca2+ mobilization. 4. Reducing the external [Ca2+] below 1 mM produced a pronounced fall in [Ca2+](i) and force. Changes in [Ca2+](i), produced by alteration of external [Ca2+] (Ca-o(2+)) were used to examine the relation between [Ca2+](i) and tension. A linear relation was found. Alteration of pH(o) to 6.9 or 7.9 did not significantly change this relation. When the tension data were normalized to their own maxima, no shift in the tension-Ca2+ relation occurred, suggesting little or no effect of pH on the Ca2+ sensitivity of force production by the contractile proteins. 5. To determine further whether the changes in [Ca2+](i) produced by alteration of pH, could account for all the changes observed in tension, [Ca2+](i) was restored to control levels while maintaining an altered pH(o). When this was done, restoration of [Ca2+](i) led to restoration of force. Thus, in this preparation, the changes in [Ca2+](i) produced by altering pH(o) in depolarized vessels can account for the changes in vascular tone.