Exaggerated depressor response to 6-iodoamiloride in NaCl-sensitive spontaneously hypertensive rats.
The current study tested the hypothesis that NaCl-sensitive hypertension may result from increased membrane sodium channel activity. The effect of 6-iodoamiloride, and analog of the sodium channel blocker amiloride, on mean arterial pressure (MAP) was examined in conscious, freely moving NaCl-sensitive spontaneously hypertensive rats (SHR-S) fed high (8%) or normal (1%) NaCl diets. SHR-S and age-matched NaCl-resistant SHR (SHR-R) and normotensive Wistar-Kyoto (WKY) control rats were studied at 9 weeks of age after 2 weeks on either high (8%) NaCl or control (1%) NaCl diets. 6-iodoamiloride was infused intravenously in doses of 0.38 or 0.76 mg/100 g body weight, and MAP and heart rate (HR) were monitored from a femoral arterial cannula for 2 hours. The 8% NaCl diet caused a significant elevation in MAP in SHR-S but not in SHR-R or WKY. Administration of 6-iodoamiloride (both doses) produced a significant, sustained decrease in MAP in both SHR-S and SHR-R. Maximal depressor responses to high dose 6-iodoamiloride were significantly enhanced in SHR-S fed 8% NaCl (31.2 +/- 3.7 mm Hg) compared to SHR-S fed 1% NaCl (14.8 +/- 2.4 mm Hg) or SHR-R fed either 8% or 1% NaCl diets (15.6 +/- 4.2 and 10.2 +/- 3.0 mm Hg, respectively). In contrast, feeding an 8% NaCl diet had no significant effect on the depressor responses to 6-iodoamiloride in either SHR-R or WKY rats. In WKY, these doses of 6-iodoamiloride had no significant effect on MAP in either diet group. 6-iodoamiloride had no significant effect on heart rate in any group. These results support the hypothesis that the exacerbation of hypertension in SHR-S fed a high NaCl diet may result from increased membrane sodium channel activity.
Chen
Y F
YF
Department of Medicine, University of Alabama, Birmingham 35294.
Yang
R H
RH
Jin
H
H
Wyss
J M
JM
Cragoe
E J
EJ
Oparil
S
S
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology*
D007473:Ion Channels; D012965:Sodium Chloride; C029230:6-iodoamiloride; D000584:Amiloride; D012964:Sodium