Ionic effects of angiotensin II and their role in the activation of the Na+/H+ antiporter.
The possible interdependence of the effects of angiotensin II (Ang II) on intracellular pH (pHi), free cytosolic calcium (Cai2+) and free cytosolic sodium (Nai+) was studied in cultured vascular smooth muscle cells (VSMC) from rat aorta. Cells were loaded with either BCECF/AM, SBFI/AM or Fura-2 for measurement of pHi, Nai+ or Cai2+, respectively. Superfusing with a HEPES solution containing Ang II (1 microM) caused a progressive increase in Nai+. Concurrent pHi changes measured in parallel experiments showed that Ang II caused a brief cell acidification followed by a delayed alkalinization, which is due to activation of the Na+/H+ antiporter. Concurrent Cai2+ changes measured in parallel experiments showed that Ang II caused a prompt rise in Cai2+ with a peak response at approximately 30 seconds followed by a rapid recovery. Obliteration of the Ang II-induced rise in Cai2+ using a Ca2+ chelator (BAPTA), prevented the initial cell acidification but did not prevent the delayed rise in pHi, which reflects stimulation of the Na+/H+ antiporter. Our data thus show that in cultured VSMC neither the rise in Cai2+ nor the fall in pHi caused by Ang II is a total prerequisite for activation of the Na+/H+ antiporter by this agonist.
Flores
G
G
Department of Medicine, Northwestern University Medical School, Chicago, Illinois, USA.
Ye
M
M
LaPointe
M
M
Batlle
D
D
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016257:Fura-2; D006863:Hydrogen-Ion Concentration; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D002614:Chelating Agents; D017923:Sodium-Hydrogen Exchangers; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D016257:Fura-2