Inhibition of adenosine-1 receptor-mediated preglomerular vasoconstriction in AT1A receptor-deficient mice.
The effect of the adenosine type 1 receptor agonist N6-cyclohexyladenosine (CHA) on glomerular vascular reactivity was studied in male angiotensin II type 1A (AT1A) receptor knockout mice (9). Vascular reactivity was assessed as the response of stop-flow pressure (PSF) to infusion of CHA into loops of Henle using micropuncture techniques. In AT1A +/+ mice at ambient arterial blood pressure (96.7 +/- 2.8 mmHg), the presence of CHA (10 (-5) M) in the perfusate increased PSF responses from 6.8 +/- 0.6 to 14.3 +/- 0.9 mmHg when the loop of Henle of the index nephron was perfused and from 0.7 +/- 0.3 to 12.3 +/- 1.0 mmHg when the loop of an adjacent nephron was perfused. At reduced arterial blood pressure (82.8 +/- 1. 3 mmHg), index nephron perfusion with CHA increased PSF responses from 4.5 +/- 0.3 to 9.4 +/- 0.4 mmHg. In AT1A -/- mice with a mean arterial blood pressure of 80 +/- 1.9 mmHg, CHA increased PSF responses only from 0.1 +/- 0.3 to 3.6 +/- 0.54 mmHg during index nephron perfusion and from 0.25 +/- 0.2 to 2.7 +/- 0.55 mmHg during adjacent nephron perfusion, significantly less than in wild-type animals (P < 0.001). Responses to CHA were intermediate in AT1A +/- mice. Thus AT1A receptor knockout mice show a markedly reduced constrictor response to CHA both in the presence and absence of simultaneous activation of the tubuloglomerular feedback system. These data support the notion of a functional interaction between adenosine and angiotensin II in the regulation of afferent arteriolar tone.
Traynor
T
T
Departments of Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Yang
T
T
Huang
Y G
YG
Arend
L
L
Oliverio
M I
MI
Coffman
T
T
Briggs
J P
JP
Schnermann
J
J
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D007678:Kidney Glomerulus / Q000098:blood supply*; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010477:Perfusion; D011312:Pressure; D012333:RNA, Messenger / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000172:deficiency* / Q000235:genetics; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*; D014666:Vasomotor System / Q000187:drug effects
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D018047:Receptors, Purinergic P1; C027513:N(6)-cyclohexyladenosine; D000241:Adenosine