Inhibition of adenosine-1 receptor-mediated preglomerular vasoconstriction in AT(1A) receptor-deficient mice

Timothy Traynor, Tianxin Yang, Yuning G. Huang, Lois Arend, Michael I. Oliverio, Thomas Coffman, Josie P. Briggs, Jürgen Schnermann

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of the adenosine type I receptor agonist N6- cyclohexyladenosine (CHA) on glomerular vascular reactivity was studied in male angiotensin II type 1A (AT(1A)) receptor knockout mice (9). Vascular reactivity was assessed as the response of stop-flow pressure (P(SF)) to infusion of CHA into loops of Henle using micropuncture techniques. In AT(1A) +/+ mice at ambient arterial blood pressure (96.7 ± 2.8 mmHg), the presence of CHA(10-5 M) in the perfusate increased P(SF) 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 P(SF) responses from 4.5 ± 0.3 to 9.4 ± 0.4 mmHg. In AT(1A) -/- mice with a mean arterial blood pressure of 80 ± 1.9 mmHg, CHA increased P(SF) 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 AT(1A) +/- mice. Thus AT(1A) 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.

Original languageEnglish (US)
Pages (from-to)F922-F927
JournalAmerican Journal of Physiology - Renal Physiology
Volume275
Issue number6 44-6
StatePublished - Dec 1998

Keywords

  • Adenosine type 1 receptor
  • Angiotensin II type 1A receptor
  • Gene knockout
  • Micropuncture
  • Mouse
  • Tubuloglomerular feedback

ASJC Scopus subject areas

  • Physiology
  • Urology

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