Exaggerated depressor response to 6-iodoamiloride in NaCl-sensitive spontaneously hypertensive rats.

Abstract

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.

• Authors: Y F Chen, R H Yang, H Jin, J M Wyss, E J Cragoe, S Oparil
• Journal: The American journal of the medical sciences (Am J Med Sci) Vol. 296 Issue 1 Pg. 78-83 (Jul 1988) ISSN: 0002-9629 [Print] United States
• PMID: 2457316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ion Channels
• Sodium Chloride
• 6-iodoamiloride
• Amiloride
• Sodium

Topics

• Amiloride (analogs & derivatives, pharmacology)
• Animals
• Blood Pressure (drug effects)
• Depression, Chemical
• Heart Rate (drug effects)
• Hypertension (etiology, metabolism)
• Ion Channels (drug effects)
• Male
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Sodium (metabolism)
• Sodium Chloride (pharmacology)