Sodium-proton (Na+/H+) exchange inhibition increases blood pressure in spontaneously hypertensive rat.
The current study was designed to determine the role of sodium-proton (Na+/H+) exchange in blood pressure regulation in sodium chloride (NaCl)-sensitive and NaCl-resistant spontaneously hypertensive rats and control Wistar-Kyoto rats (WKY) using 5-(N,N-hexamethylene)amiloride (HMA), a potent and selective inhibitor of Na+/H+ exchange. The response of mean arterial pressure to intravenous infusion of HMA was examined in conscious, unrestrained male rats maintained on normal (1%) or high (8%) NaCl diets for 3 weeks beginning at age 7 weeks. The HMA significantly increased mean arterial pressure in NaCl-sensitive spontaneously hypertensive rats and NaCl-resistant spontaneously hypertensive rats that were fed 1% NaCl, but not in WKY rats that were fed 1% NaCl; the 8% NaCl diet enhanced this pressor response in all 3 strains. The pressor response was accompanied by significant increases in plasma norepinephrine levels in NaCl-sensitive spontaneously hypertensive rats on both diets, but not in NaCl-resistant spontaneously hypertensive rats or WKY rats on either diet. There were no differences in steady-state levels (30-60 nM) of plasma HMA between diet groups in any strain. Therefore, administration of HMA in a dose at which it is highly selective for the Na+/H+ exchanger (Ki = 160 nM) caused a systemic pressor response in spontaneously hypertensive rats that was enhanced by dietary NaCl supplementation. With these data, it is suggested that inhibition of Na+/H+ exchange in vivo has a pressor effect greater in spontaneously hypertensive rats than in WKY rats and is further enhanced by NaCl supplementation.
Chen
Y F
YF
Department of Medicine, University of Alabama at Birmingham 35294.
Yang
R H
RH
Meng
Q C
QC
Cragoe
E J
EJ
Oparil
S
S
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012965:Sodium Chloride / Q000494:pharmacology; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000502:physiology
D017673:Sodium Chloride, Dietary; D017923:Sodium-Hydrogen Exchangers; C057360:5-(N,N-hexamethylene)amiloride; D012965:Sodium Chloride; D000584:Amiloride; D009638:Norepinephrine