Adenosine A1‐receptor knockout mice have a decreased blood pressure response to low dose angiotensin II (Ang II) infusion.

Adenosine, acting on A1‐receptors (A1‐AR) in the nephron, increases sodium reabsorption and also increases renal vascular resistance (RVR), via A1‐AR in the afferent arteriole. Ang II, which also increases RVR and decreases renal blood flow, stimulates adenosine release in the kidney. We tested the hypothesis that the Ang II slow pressor response is dependent on A1‐ARs. Mean arterial pressure (MAP) was measured by radiotelemetry in A1‐AR knockout mice (KO) and their wild‐type (WT) controls, before and during Ang II (400 ng/kg/min) infusion. Animals were placed in metabolic cages for 24‐hour urine collections. Baseline MAP was lower in KO mice (KO:102±2 vs WT:113±1 mmHg, p<0.05). Ang II increased MAP in both groups, but on day 12 MAP was lower in A1‐AR KO mice (KO: 109±5 vs 126±7 mmHg, p<0.01). Heart rates were not different. Basal sodium excretion was not different (KO: 0.16±0.07 vs WT: 0.13±0.04 mmol/day) but was higher in KO mice 12 days after Ang II despite a lower MAP (KO: 0.21±0.02 vs WT: 0.12±0.04 mmol/day, p<0.05). These results indicate that the A1‐AR is required to increase MAP during low dose Ang II‐infusion by limiting Na+ excretion. This study suggests that A1‐AR antagonists might be effective anti‐hypertensive agents in Ang II and volume‐dependent hypertension.