Journal
HYPERTENSION
Volume 72, Issue 2, Pages 511-521Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.117.10765
Keywords
adenosine; adenosine receptors; blood pressure; Dahl salt-sensitive rats; hypertension
Categories
Funding
- National Institutes of Health [DK091190, HL069846, DK068575, HL109002, DK079307]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R24HL114474, R01HL069846, R01HL109002] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK079307, R01DK091190, R01DK068575] Funding Source: NIH RePORTER
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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.
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