Differential regulation of norepinephrine- and prostaglandin F-2 alpha-induced contraction by extracellular Na+ in rat aorta

The purpose of this study was to test whether extracellular Na+ differentia lly regulates agonist-induced contraction in vascular smooth muscle. Exposu re of rat aorta to 20 mM extracellular Na+ by substitution of 123 mM Na+ wi th N-methyl-D-glucamine or choline, inhibited norepinephrine-induced contra ction to a greater magnitude than contraction to prostaglandin F-2 alpha. I n the absence of extracellular Ca2+ and in 20 mM Na+ solution containing 12 3 mM N-methyl-D-glucamine, the norepinephrine and prostaglandin F-2 alpha c ontraction remained unaltered. In contrast, in the absence of extracellular Ca2+ and in 20 mM Na+ solution containing 123 mM choline, the norepinephri ne and prostaglandin F-2 alpha contraction were decreased and increased, re spectively. Contraction to the phorbol ester, phorbol dibutyrate, was inhib ited in 20 mM extracellular Na+ solution containing N-methyl-D-glucamine. R emoval of extracellular Ca2+ inhibited the phorbol dibutyrate contraction, and 20 mM exuacellular Na+ solution containing N-methyl-D-glucamine did not inhibit the phorbol dibutyrate contraction elicited in the absence of extr acellular Ca2+. Complete replacement of extracellular Na+ with choline, and concomitant treatment with nifedipine to reduce the elevated basal tone af ter Na+ replacement, also resulted in greater inhibition of norepinephrine- as compared with prostaglandin F-2 alpha-induced contraction. Ethylisoprop ylamiloride, a Na+/H+ exchange inhibitor, did not alter norepinephrine cont raction, as determined in the presence of nifedipine to reduce the elevated basal tone due to ethylisopropylamiloride. Acidification, which may result from decreased Na+/H+ exchange, inhibited the prostaglandin F-2 alpha-indu ced contraction to a greater magnitude than contraction to norepinephrine. These results demonstrate that extracellular Na+ selectively regulates agon ist-induced contraction. The study further suggests that the selectivity ma y be related to an extracellular Na+-dependent process that is activated by protein kinase C, such as Na+/Ca2+ exchange, and is unrelated to the relea se of intracellular Ca2+ and Na+/H+ exchange.