Adenosine Receptors Influence Hypertension in Dahl Salt-Sensitive Rats: Dependence on Receptor Subtype, Salt Diet, and Sex

The influence of adenosine receptors on blood pressure in salt-sensitive hypertension is unknown. Here, we examined the effects of salt diets on arterial blood pressures (radiotelemetry) in female and male Dahl salt-sensitive wild-type versus female and male Dahl salt-sensitive A(1), A(2A), or A(2B) receptor knockouts (A(1)KOs, A(2A)KOs, and A(2B)KOs, respectively). At baseline, all rats were on a 0.3% salt diet; then separate groups were switched to either 4% or 8% salt diet for 2 weeks. Compared with wild-types, baseline pressures were not affected by knockout of A(1) or A(2B) receptors; yet, mean, systolic, and diastolic pressures were significantly (P<0.01) higher in A(2A)KOs versus wild-types, an effect independent of sex. During the second week on a 4% salt diet, mean, systolic, and diastolic blood pressures (mmHg, mean +/- SEM) in female A(1)KOs (176 +/- 5, 209 +/- 5, and 147 +/- 4, respectively) and A(2B)KOs (166 +/- 8, 198 +/- 9, and 139 +/- 8, respectively) were significantly lower (P<0.001) than wild-type on a 4% salt diet (202 +/- 4, 240 +/- 5, and 172 +/- 3, respectively). Male A(1)KOs and A(2B)KOs were not protected against 4% salt diet-induced hypertension. This female advantage was overwhelmed by an 8% salt diet. Female and male A(2A)KOs were more salt sensitive, a phenotype that was apparent in male A(2A)KOs on 4% and 8% salt diets and in females on 8% salt diet. Female A(1)KOs and A(2B)KOs were less susceptible to salt-induced stroke and experienced improved survival. Adenosine receptors influence blood pressure and survival in salt-sensitive rats, and the impact of deleting adenosine receptors on blood pressure and survival depends on salt diet and sex.