Adenosine Receptors Influence Hypertension in Dahl Salt-Sensitive Rats

Abstract

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, A, or A receptor knockouts (AKOs, AKOs, and AKOs, 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 or A receptors; yet, mean, systolic, and diastolic pressures were significantly (<0.01) higher in AKOs versus wild-types, an effect independent of sex. During the second week on a 4% salt diet, mean, systolic, and diastolic blood pressures (mm Hg, mean±SEM) in female AKOs (176±5, 209±5, and 147±4, respectively) and AKOs (166±8, 198±9, and 139±8, respectively) were significantly lower (<0.001) than wild-type on a 4% salt diet (202±4, 240±5, and 172±3, respectively). Male AKOs and AKOs were not protected against 4% salt diet-induced hypertension. This female advantage was overwhelmed by an 8% salt diet. Female and male AKOs were more salt sensitive, a phenotype that was apparent in male AKOs on 4% and 8% salt diets and in females on 8% salt diet. Female AKOs and AKOs 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.

Targeting the Gut Microbiota to Investigate the Mechanism of Lactulose in Negating the Effects of a High‐Salt Diet on Hypertension

“…HSDs are an important research topic and are generally recognized to cause hypertension . However, humans continue to consume HSDs.…”

Adenosine, Via A 2B Receptors, Inhibits Human (P-SMC) Progenitor Smooth Muscle Cell Growth

“…This strongly suggests that A 2B -receptor agonists would counteract the vascular remodeling process associated with occlusive disorders in a sex-independent fashion. Nonetheless, as sex differences in adenosine responses are known to occur, 34 in vivo experiments are required to confirm our in vitro findings of sex independence.…”

Focusing on Adenosine Receptors as a Potential Targeted Therapy in Human Diseases

“…In fact, KO mice have normal blood pressure [242]. Recently, the deletion of A 2B AR was shown to protect against salt-induced hypertension and stroke [243] and inhibit increases in mean arterial blood pressure [244].…”