ANG-II DEPENDENCE OF TUBULOGLOMERULAR FEEDBACK RESPONSIVENESS IN HYPERTENSIVE REN-2 TRANSGENIC RATS

K D MITCHELL, John Mullins

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Abstract

The present study was performed to determine the angiotensin II (ANG II) dependence of stop-flow pressure (SFP) tubuloglomerular feedback responses in hypertensive transgenic rats [strain name: TGR(mRen2)27] harboring the mouse ren-2 renin gene. SFP feedback responses to increases in late proximal perfusion rate were assessed in pentobarbital-anesthetized male ren-2 transgenic rats during control conditions and after administration of the AT(1) receptor antagonist, L-158,809 (1 mg/kg iv). During control conditions, increases in late proximal perfusion rate elicited flow-dependent decreases in SFP. The magnitude of the maximal SFP feedback response to a late proximal perfusion rate of 40 nl/min averaged 16.1 +/- 1.4 mmHg (n = 7), a value higher than that normally observed in normotensive rats. Administration of L-158,809 decreased mean arterial blood pressure (174 +/- 6 vs. 117 +/- 4 mmHg, P < 0.01, n = 10) and attenuated the magnitude of the maximal SFP feedback response by 84 +/- 4% (16.1 +/- 1.4 vs. 2.6 +/- 0.5 mmHg, P < 0.01, n = 7). In contrast, mechanical reduction of renal arterial pressure from 179 +/- 5 to 113 +/- 1 mmHg (P < 0.01, n = 7) attenuated the magnitude of the maximal SFP feedback response by only 43 +/- 5% (14.4 +/- 1.9 vs. 7.9 +/- 0.7 mmHg, P < 0.01, n = 7), indicating that approximately one-half of the attenuation of SFP feedback responses elicited by AT(1) receptor blockade was due to removal of the stimulatory effect of ANG II on the sensitivity of the tubuloglomerular feedback mechanism. The present findings indicate that the tubuloglomerular feedback mechanism in ren-a transgenic rats is intact and that ANG II, acting via AT(1) receptors, exerts a significant stimulatory influence on the responsiveness of the preglomerular contractile elements that mediate glomerular capillary pressure feedback responses in ren-2 transgenic rats.

Original languageEnglish
Pages (from-to)F821-F828
Number of pages8
JournalAmerican Journal of Physiology - Renal Physiology
Volume37
Issue number5
Publication statusPublished - May 1995

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