Increased contractile response induced with ouabain is abolished by thapsigargin in aorta of renal hypertensive rats.
1. The aim of the present study was to test in vitro if the increased contractile effect of phenylephrine and KCl, observed after the addition of ouabain in renal hypertensive rat aorta, is mediated by Ca2+ accumulated on the sarcoplasmic reticulum. 2. In aortas of one kidney (1K) rats, ouabain did not modify the concentration-effect curves stimulated with phenylephrine and KCl. 3. Contractile responses stimulated with phenylephrine and KCl were potentiated by ouabain in one kidney--one clip (1K-1C) aortas, and preincubation with thapsigargin abolished the increasing effect of ouabain on these contractions. 4. The addition of thapsigargin before phenylephrine and KCl did not modify the contractile response to phenylephrine and KCl or the resting vascular tone during the time incubation. 5. In the presence of ouabain, thapsigargin significantly increased the vascular tone only in 1K-1C rat aortas. 6. Increased intracellular Na+ concentration as a consequence of Na(+)-K(+)-ATPase inhibition induces increased accumulation of Ca2+ inside the sarcoplasmic reticulum in 1K-1C rat aortas. The differential effects in renal hypertensive and normotensive aortas suggest a possible role of this mechanism in modulating cytosolic Ca2+ in renal hypertension.
Ceron
P I
PI
Laboratory of Pharmacology, College of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, Brazil.
Bendhack
L M
LM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006977:Hypertension, Renal / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010042:Ouabain / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D010042:Ouabain; D011189:Potassium Chloride; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases