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Am J Physiol Regul Integr Comp Physiol 285: R44-R49, 2003; doi:10.1152/ajpregu.00739.2002
0363-6119/03 $5.00
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LOCAL CONTROL OF CIRCULATION

Attenuated renovascular constrictor responses to angiotensin II in adenosine 1 receptor knockout mice

Pernille B. Hansen, Seiji Hashimoto, Josie Briggs, and Jurgen Schnermann

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892

Submitted 4 December 2002 ; accepted in final form 20 February 2003

In the present experiments we examined the renovascular constrictor effects of ANG II in the chronic and complete absence of A1 adenosine receptors (A1AR) using mice with targeted deletion of the A1AR gene. Glomerular filtration rate (GFR) was not different between A1AR +/+ and A1AR -/- mice under control conditions (450.5 ± 60 vs. 475.2 ± 62.5 µl/min) but fell significantly less in A1AR -/- mice during infusion of ANG II at 1.5 ng/min (A1AR +/+: 242 ± 32.5 µl/min, A1AR -/-: 371 ± 42 µl/min; P = 0.03). Bolus injection of 1, 10, and 100 ng of ANG II reduced renal blood flow and increased renal vascular resistance significantly more in A1AR +/+ than in A1AR -/- mice. Perfused afferent arterioles isolated from A1AR +/+ mice constricted in response to bath ANG II with an EC50 of 1.5 ± 0.4 x 10-10 mol/l, whereas a right shift in the dose-response relationship with an EC50 of 7.3 ± 1.2 x 10-10 mol/l (P < 0.05) was obtained in arterioles from A1AR -/- mice (P < 0.05). The expression of AT1A receptor mRNA was not different in kidney RNA from A1AR +/+ or A1AR -/- mice. We conclude that chronic A1AR deficiency diminishes the effectiveness of ANG II to constrict renal resistance vessels and to reduce GFR.

renal blood flow; ultrasonic flowmeter; renal vascular resistance; glomerular filtration rate; perfused arterioles


Address for reprint requests and other correspondence: J. Schnermann, NIDDK, NIH, Bldg. 10, Rm. 4 D51, 10 Center Dr. MSC 1370, Bethesda, MD (E-mail: jurgens{at}intra.niddk.nih.gov).




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