Compromised renal microvascular reactivity of angiotensin type 1 double null mice.
Angiotensin type 1A (AT(1A)) and 1B (AT(1B)) receptor deletion (AT1DKO) results in renal microvascular disease, tubulointerstitial injury, and reduced blood pressure. To test the hypothesis that renal preglomerular responses to angiotensin (ANG) II are mediated by AT(1A) and AT(1B) receptors, experiments were performed in AT1DKO mice using the in vitro blood perfused juxtamedullary nephron technique. Kidneys were harvested from AT1DKO and wild-type (WT) mice and bathed with ANG II (1-100 nM), norepinephrine (NE; 100-1,000 nM), or acetylcholine (ACh; 10 microM). Baseline diameters of afferent (19.5 +/- 0.7 and 13.9 +/- 0.7 microm, n = 17 and 16) and efferent (15.5 +/- 2.1 and 10.8 +/- 1.0 microm, n = 4 and 7) arterioles of AT1DKO were significantly larger than WT. Afferent and efferent arteriolar responses to ANG II, 100, and 300 nM NE were absent in AT1DKO; although significant constriction to 1 microM NE was observed (-17 +/- 5 and -23 +/- 6%, respectively). Afferent arterioles of WT mice dilated significantly in response to ACh (15.1 +/- 0.6 to 17.0 +/- 1.2 microm, n = 6); however, arterioles from AT1DKO tended to contract (19.9 +/- 1.2 to 17.8 +/- 1.6 microm; n = 6, P = 0.06). In summary, loss of ANG II-induced contraction, reduced vasoconstriction to NE, and endothelial cell dysfunction contribute to the renal vascular phenotype of AT1DKO mice. We conclude that ANG II signaling via the AT(1) receptor plays a pivotal role in basal renal microvascular tone and effectiveness to respond to vasoconstrictor and vasodilator agonists.
Park
Sungmi
S
Dept. of Physiology, Louisiana State University Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112, USA.
Bivona
Benjamin J
BJ
Harrison-Bernard
Lisa M
LM
D000109:Acetylcholine / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000502:physiology; D007150:Immunohistochemistry; D007668:Kidney / Q000033:anatomy & histology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism; D009399:Nephrons / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000199:Actins; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000109:Acetylcholine; D009638:Norepinephrine