Inhibition of adenosine1 receptor-mediated glomerular vasoconstriction in AT1A-receptor deficient mice
Previous studies have shown that tubuloglomerular feedback (TGF) responses are virtually abolished in angiotensin II 1A (AT1A) receptor null mutant mice (Ito et al., PNAS 1995). Since adenosine is a potential mediator of TGF-induced constriction we examined the effect of the adenosine1-receptor agonist cyclohexyladenosine (CHA) on glomerular vascular reactivity in the AT1A knockout mice. Vascular reactivity was assessed as the response of stop flow pressure (PSF) to infusion of CHA into loops of Henle using micropuncture techniques. Animals were genotyped by PCR with primers amplifying sequences from the deleted AT1A gene and from the neomycin resistance gene. In AT1A +/+ mice, CHA (10-5 M) increased PSF responses from 6.8 ± 0.6 to 14.3 ± 0.9 mm Hg when the loop of Henle of the index nephron was perfused, and from 0.7 ± 0.3 to 12.3 ± 1.0 mm Hg when the loop of an adjacent nephron was perfused. In AT1A -/- mice, CHA increased PSF responses only from 0.1 ± 0.3 to 3.6 ± 0.54 mm Hg, and from 0.25 ± 0.2 to 2.7 ± 0.55 mm Hg during perfusion of the index nephron or adjacent nephron respectively (p<0.001 compared to control animals). Responses to CHA were intermediate in AT1A +/- mice. Absence of TGF responses and abnormally low constrictor effects of CHA both with and without simultaneous activation of the TGF system are consistent with the notion that adenosine plays a critical role in TGF responsiveness.
Duke Scholars
Published In
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Biochemistry & Molecular Biology
- 3208 Medical physiology
- 3101 Biochemistry and cell biology
- 1116 Medical Physiology
- 0606 Physiology
- 0601 Biochemistry and Cell Biology
Citation
Published In
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Biochemistry & Molecular Biology
- 3208 Medical physiology
- 3101 Biochemistry and cell biology
- 1116 Medical Physiology
- 0606 Physiology
- 0601 Biochemistry and Cell Biology