title: Differential regulation of norepinephrine- and prostaglandin F2alpha-induced contraction by extracellular Na+ in rat aorta.
abstract: The purpose of this study was to test whether extracellular Na+ differentially regulates agonist-induced contraction in vascular smooth muscle. Exposure of rat aorta to 20 nM extracellular Na+ by substitution of 123 mM Na+ with N-methyl-D-glucamine or choline, inhibited norepinephrine-induced contraction to a greater magnitude than contraction to prostaglandin F2alpha. In the absence of extracellular Ca2+ and in 20 mM Na+ solution containing 123 mM N-methyl-D-glucamine, the norepinephrine and prostaglandin F2alpha contraction remained unaltered. In contrast, in the absence of extracellular Ca2+ and in 20 mM Na+ solution containing 123 mM choline, the norepinephrine and prostaglandin F2alpha contraction were decreased and increased, respectively. Contraction to the phorbol ester, phorbol dibutyrate, was inhibited in 20 mM extracellular Na+ solution containing N-methyl-D-glucamine. Removal of extracellular Ca2+ inhibited the phorbol dibutyrate contraction, and 20 mM extracellular Na+ solution containing N-methyl-D-glucamine did not inhibit the phorbol dibutyrate contraction elicited in the absence of extracellular Ca2+. Complete replacement of extracellular Na+ with choline, and concomitant treatment with nifedipine to reduce the elevated basal tone after Na+ replacement, also resulted in greater inhibition of norepinephrine- as compared with prostaglandin F2alpha-induced contraction. Ethylisopropylamiloride, a Na+/H+ exchange inhibitor, did not alter norepinephrine contraction, 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 F2alpha-induced contraction to a greater magnitude than contraction to norepinephrine. These results demonstrate that extracellular Na+ selectively regulates agonist-induced contraction. The study further suggests that the selectivity may 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 release of intracellular Ca2+ and Na+/H+ exchange.
authors.affiliation: Veterans Affairs Medical Center and the Department of Pharmacology & Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0575, USA. robert.rapoport@uc.edu
authors.forename: R M
authors.initials: RM
authors.lastname: Rapoport
authors.forename: A K
authors.initials: AK
authors.lastname: Campbell
authors.forename: K C
authors.initials: KC
authors.lastname: Chang
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006531:HEPES / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000584:Amiloride; D012964:Sodium; D015237:Dinoprost; D006531:HEPES; D002118:Calcium; C039614:ethylisopropylamiloride; D009638:Norepinephrine