Renal segmental microvascular responses to ANG II in AT1A receptor null mice.
The relative contributions of AT(1A) and AT(1B) receptors to afferent arteriolar autoregulatory capability and afferent and efferent arteriolar responses to ANG II are not known. Experiments were conducted in kidneys from wild-type (WT) and AT(1A)-/- mice utilizing the in vitro blood-perfused juxtamedullary nephron technique. Direct measurements of afferent (AAD) and efferent arteriolar diameters (EAD) were assessed at a renal arterial pressure of 100 mmHg. AAD averaged 14.8 +/- 0.8 microm for WT and 14.9 +/- 0.8 microm for AT(1A)-/- mice. AAD significantly decreased by 7 +/- 1, 16 +/- 1, and 26 +/- 2% for WT mice and by 11 +/- 1, 20 +/- 2, and 30 +/- 3% for AT(1A)-/- mice (120, 140, 160 mmHg). AAD autoregulatory capability was not affected by the absence of AT(1A) receptors. AAD responses to 10 nM ANG II were significantly blunted for AT(1A)-/- mice compared with WT (-22 +/- 2 vs. -37 +/- 5%). ANG II (0.1-10 nM) failed to elicit any change in EAD for AT(1A)-/- mice. AAD and EAD reductions in ANG II were blocked by 1 microM candesartan. We conclude that afferent arteriole vasoconstrictor responses to ANG II are mediated by AT(1A) and AT(1B) receptors, whereas efferent arteriolar vasoconstrictor responses to ANG II are mediated by only AT(1A) receptors in the mouse kidney.
Harrison-Bernard
Lisa M
LM
Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA. lharris@tulane.edu
Cook
Anthony K
AK
Oliverio
Michael I
MI
Coffman
Thomas M
TM
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply* / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D009399:Nephrons / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000172:deficiency* / Q000235:genetics; D013777:Tetrazoles / Q000494:pharmacology; D014654:Vascular Patency / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C081643:candesartan