Hypertension II: Hypertension and Vascular Control

Re: Dietary salt and arteriolar responsiveness

Julian H. Lombard

On Tue Dec 8, Matt Boegehold wrote
>Thanks for presenting these very interesting findings. Do you think that reduced arteriolar responsiveness in normotensive rats fed high salt for 4-6 weeks might also be linked to reduced endogenous AII activity? Is there a compensatory increase in arteriolar responsiveness to AII during this more chronic suppression of AII, and if so, how might this influence arteriolar responses to ACh, hypoxia and iloprost?

>Matt Boegehold  


Thanks for your question.  I believe that the reduced responsiveness of animals fed a high salt diet for 4-6 weeks is probably due to AngII suppression as well.  Rieder et al. (Hypertension 30:  120-127) demonstrated that AngII levels were still suppressed in reduced renal mass rats that were on a chronic high salt diet. If AII is an important factor regulating vasodilator reactivity, suppression of AII could still be the major factor mediating the impaired vasodilator response.  We have observed that infusion of low doses of AngII for the 3 day time period restores normal vasodilator responses in skeletal muscle resistance arteries and middle cerebral arteries, and presumably it would work the same way in arterioles.  The technical difficulties of chronically infusing AngII over a 4-6 week period have prevented us from conducting those experiments, but the effect of AngII restoration would presumably be the same.  

Your question about the effect of chronic high salt diet on AngII responsiveness leads us into some interesting territory. Earlier studies (e.g., the work of Catt and coworkers) have indicated that vascular responsiveness to Ang II is enhanced by Na+ loading and depressed by Na restriction, and that these differences appear to be mediated by changes in the expression of AngII receptors.  That is, the receptor number in the vascular tissue (mesenteric artery in that study) increased with Na+ loading, although the change in receptor density in other tissues did not necessarily follow the same pattern.

We have observed that the vasoconstrictor responsiveness to AngII is enhanced in skeletal muscle resistance arteries of animals on a chronic high salt diet, but this is not the case in the arterioles.  In addition, the changes in AngII responsiveness do not occur in the animals subjected to short term elevations in dietary salt intake. This is important, because it demonstrates that altered  responsiveness to the vasoconstrictor effects of AngII does not occur as rapidly as the impaired vasodilator response.  Finally, the enhanced vasoconstrictor response is specific for AngII, because the constriction of the vessels in response to norepinephrine, and the myogenic response to transmural pressure elevation is not potentiated in the animals on short term or chronic high salt diet.

If the protective effect of AngII restoration is mediated via interaction of AngII with its receptors in the vascular wall, and AngII receptors are increased with chronic salt loading, it is conceivable that chronic elevations in dietary salt intake may have a less severe effect in depressing vasodilator responsiveness.  However, based on our existing data, it does not appear that any change in AngII responsiveness is sufficient to restore any degree of normal vasodilator reactivity in the resistance arteries.

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