Reduced autoregulatory effectiveness in adenosine 1 receptor-deficient mice.
Adjustments of renal vascular resistance in response to changes in blood pressure are mediated by an interplay between the myocyte-inherent myogenic and the kidney-specific tubuloglomerular feedback (TGF) mechanisms. Using mice with deletion of the A(1) adenosine receptor (A1AR) gene, we tested the prediction that the absence of TGF, previously established to result from A1AR deficiency, is associated with a reduction in the efficiency of autoregulation. In anesthetized wild-type (A1AR+/+) and A1AR-deficient mice (A1AR-/-), glomerular filtration rate (GFR) and renal blood flow (RBF) were determined before and after reducing renal perfusion pressure through a suprarenal aortic clamp. In response to a blood pressure reduction by 15.9 +/- 1.34 mmHg in A1AR-/- (n = 9) and by 14.2 +/- 0.9 mmHg in A1AR+/+ mice (n = 8; P = 0.31), GFR fell by 187.9 +/- 37 mul/min and by 72.3 +/- 10 mul/min in A1AR-/- and A1AR+/+ mice, respectively (P = 0.013). Similarly, with pressure reductions of 14.8 +/- 1.1 and 13.3 +/- 1.5 mmHg in A1AR-/- (n = 9) and wild-type mice (n = 8), respectively (P = 0.43), RBF fell by 0.17 +/- 0.02 ml/min in A1AR-/- mice and by only 0.08 +/- 0.02 ml/min in wild-type animals (P = 0.0039). Autoregulatory indexes for both GFR and RBF were significantly higher in A1AR-/- compared with A1AR+/+ mice, indicating reduced regulatory responsiveness in the knockout animals. We conclude that autoregulation of renal vascular resistance is less complete in A1AR-deficient mice, an effect that is presumably related to absence of TGF regulation in these animals.
Hashimoto
S
S
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Huang
Y
Y
Briggs
J
J
Schnermann
J
J
D000818:Animals; D001794:Blood Pressure; D025461:Feedback, Physiological; D005260:Female; D005919:Glomerular Filtration Rate; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043682:Receptor, Adenosine A1 / Q000235:genetics* / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology*
D043682:Receptor, Adenosine A1