title: Adenosine A1-receptor knockout mice have a decreased blood pressure response to low-dose ANG II infusion.
abstract: Adenosine, acting on A(1)-receptors (A(1)-AR) in the nephron, increases sodium reabsorption, and also increases renal vascular resistance (RVR), via A(1)-ARs in the afferent arteriole. ANG II increases blood pressure and RVR, and it stimulates adenosine release in the kidney. We tested the hypothesis that ANG II-infused hypertension is potentiated by A(1)-ARs' influence on Na(+) reabsorption. Mean arterial pressure (MAP) was measured by radiotelemetry in A(1)-AR knockout mice (KO) and their wild-type (WT) controls, before and during ANG II (400 ng·kg(-1)·min(-1)) infusion. Baseline MAP was not different between groups. ANG II increased MAP in both groups, but on day 12, MAP was lower in A(1)-AR KO mice (KO: 128 ± 3 vs. 139 ± 3 mmHg, P < 0.01). Heart rates were significantly different during days 11-14 of ANG II. Basal sodium excretion was not different (KO: 0.15 ± 0.03 vs. WT: 0.13 ± 0.04 mmol/day, not significant) but was higher in KO mice 12 days after ANG II despite a lower MAP (KO: 0.22 ± 0.03 vs. WT: 0.11 ± 0.02 mmol/day, P < 0.05). Phosphate excretion was also higher in A(1)-AR KO mice on day 12. Renal expression of the sodium-dependent phosphate transporter and the Na(+)/glucose cotransporter were lower in the KO mice during ANG II treatment, but the expression of the sodium hydrogen exchanger isoform 3 was not different. These results indicate that the increase in blood pressure seen in A(1)-AR KO mice is lower than that seen in WT mice but was increased by ANG II nonetheless. The presence of A(1)-ARs during a low dose of ANG II-infusion limits Na(+) and phosphate excretion. This study suggests that A(1)-AR antagonists might be an effective antihypertensive agent during ANG II and volume-dependent hypertension.
authors.affiliation: Department of Physiology and Biophysics, Howard University, Washington, DC, USA.
authors.forename: Dexter L
authors.initials: DL
authors.lastname: Lee
authors.forename: Tracy D
authors.initials: TD
authors.lastname: Bell
authors.forename: Jenny
authors.initials: J
authors.lastname: Bhupatkar
authors.forename: Glenn
authors.initials: G
authors.lastname: Solis
authors.forename: William J
authors.initials: WJ
authors.lastname: Welch
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004573:Electrolytes / Q000652:urine; D015918:Infusion Pumps, Implantable; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004573:Electrolytes; D043682:Receptor, Adenosine A1; D000804:Angiotensin II