Altered Na(+)- H(+)- exchange activity in the spontaneously hypertensive perfused rat heart.
Intracellular pH (pHi) and developed pressure during hypercapnic acidosis were studied in the spontaneously hypertensive rat (SHR) heart and Wistar-Kyoto controls. Developed pressure was determined using a modified Langendorff isovolumic perfusion technique and 31P magnetic resonance spectroscopy was used to determine pHi. In response to acidosis, both developed pressure and pHi first decreased and then partially recovered. In the SHR group, pHi during the early periods of acidosis was significantly higher than in the control group while there was no significant difference in the steady-state pHi. The addition of 5-(N,N)-hexamethylene-amiloride (HMA), a specific inhibitor of Na(+)-H+ exchange, abolished these difference. Furthermore, HMA was found to inhibit recovery in pHi and developed pressure during acidosis in both groups. These results demonstrate that Na(+)-H(+)-exchange in the rat heart plays a major role in pHi regulation and contributes to functional recovery during acidosis. In addition, Na(+)-H(+)-exchange activity, as previously found in other tissues in hypertension, is increased in the SHR heart.
Department of Biochemistry, University of Oxford, UK.
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D000138:Acidosis; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D006321:Heart / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013997:Time Factors
D017923:Sodium-Hydrogen Exchangers; C057360:5-(N,N-hexamethylene)amiloride; D002245:Carbon Dioxide; D000584:Amiloride; D012964:Sodium