Involvement of the Na+-independent Cl-/HCO3- exchange (AE) isoform in the compensation of myocardial Na+/H+ isoform 1 hyperactivity in spontaneously hypertensive rats.
Enhanced activity of Na+/H+ isoform 1 (NHE-1) and the Na+-independent Cl-/HCO3- exchange (AE) is a feature of the hypertrophied myocardium in spontaneously hypertensive rats (SHR). The present study explored the possibility that sustained intracellular acidosis due to increased myocardial acid loading through AE causes NHE-1 enhancement. To this aim, SHR were treated for 2 weeks with a rabbit polyclonal antibody against an AE3 isoform that was recently developed and proven to have inhibitory effects on myocardial AE activity. We then compared the AE activity in the left ventricle papillary muscles isolated from untreated SHR with antiAE3-treated SHR; AE activity was measured in terms of the rate of intracellular pH recovery after an intracellular alkali load was introduced. AE activity was diminished by approximately 70% in SHR treated with the antiAE3 antibody, suggesting that the AE3 isoform is a major carrier of acid-equivalent influx in the hypertrophied myocardium. However, the antibody treatment failed to normalize NHE-1 activity that remained elevated in the myocardium of normotensive rats. The data therefore rule out the possibility that NHE-1 hyperactivity in hypertensive myocardium was due to sustained intracellular acidosis induced by increased AE activity that characterizes SHR myocardial tissue.
Farias
Fernando
F
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas de La Plata, Universidad Nacional de La Plata, Argentina.
Morgan
Patricio
P
Chiappe de Cingolani
Gladys
G
Camilión de Hurtado
María C
MC
D000136:Acid-Base Equilibrium; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001794:Blood Pressure; D001835:Body Weight; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010210:Papillary Muscles / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
D000906:Antibodies; D017920:Antiporters; C489238:Slc4a3 protein, rat; C452850:Slc9a1 protein, rat; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D012313:RNA