Abstract
In aortas of spontaneously hypertensive rats (SHRs), excessive dietary salt causes down-regulation of soluble guanylate cyclase (sGC) followed by decreased cyclic GMP production, which leads to impairment of the vascular relaxation response to nitric oxide (NO). The present study aimed to elucidate whether this impaired NO/cyclic GMP system results secondarily from increased blood pressure or from an effect of the salt itself. The antihypertensive drug nifedipine was used on 4-week-old SHRs that received a normal-salt diet or a high-salt diet for 4 weeks. Treatment with nifedipine (30 mg/kg/day, p.o.) reduced the increased blood pressure of SHRs fed the high-salt diet to the level of SHRs fed the normal-salt diet. In aortic rings from SHRs fed the high-salt diet, not only endothelium-dependent relaxations but also endothelium-independent relaxations were significantly impaired. However, these impairments were not alleviated by treatment with nifedipine. Furthermore, nifedipine did not prevent the increase in protein levels of endothelial NO synthase and the decrease in the protein levels of sGC in aortas from SHRs fed the high-salt diet. These alterations by high salt intake were restored after replacement with the normal-salt diet for 4 additional weeks. These results indicate that in SHRs given excessive dietary salt, normalization of salt intake but not blood pressure reduction can ameliorate alterations in the NO/cyclic GMP system. High salt intake may directly affect the vascular smooth muscle and cause impairment of the relaxation response to NO.
Footnotes
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This work was partly supported by a grant from The Smoking Research Foundation, Japan.
- Abbreviations:
- NO
- nitric oxide
- eNOS
- endothelial NO synthase
- sGC
- soluble guanylate cyclase
- SHR
- spontaneously hypertensive rat
- NOx
- NO2− plus NO3−
- pEC50
- negative logarithm molar concentration of agonist required to produce 50% of the maximal response
- Rmax
- maximum relaxation response
- ANOVA
- analysis of variance
- PLSD
- protected least significant difference
- Received December 7, 2001.
- Accepted March 6, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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