Modulation of Tubuloglomerular Feedback by Angiotensin II Type 1 Receptors During the Development of Goldblatt Hypertension

Abstract

Abstract It has been suggested that the increased levels of angiotensin II (Ang II) in the contralateral kidney of two-kidney, one clip (2K1C) Goldblatt hypertensive rats act to enhance tubuloglomerular feedback responsiveness and proximal tubular reabsorption and thereby exert a substantial sodium-retaining influence on the nonclipped kidney. The current study investigated the Ang II dependency of tubuloglomerular feedback responsiveness in the nonclipped kidney during the early stages of development of 2K1C hypertension. Stop-flow pressure feedback responses were assessed in the nonclipped kidney of 2K1C rats during control conditions and after systemic administration of the Ang II type 1 receptor antagonist losartan (10 mg/kg). In 1-week clipped and sham-operated rats, losartan administration decreased mean arterial pressure (from 143±6 to 123±2 mm Hg, P <.01, and from 129±2 to 106±5 mm Hg, P <.01, respectively) and attenuated the magnitude of the maximal feedback responses (from −12.9±1.2 to −3.0±0.3 mm Hg, P <.01, and from −13.2±1.5 to −3.6±1.1 mm Hg, P <.01, respectively). The decreases in mean arterial pressure were not significantly different in sham-operated and 1-week clipped rats. In 3-week clipped rats, mean arterial pressure was further elevated (163±6 mm Hg) compared with sham-operated rats (134±4 mm Hg, P <.01). Although maximal tubuloglomerular feedback responses were similar in 3-week clipped and sham-operated rats, the late proximal perfusion rate eliciting a half-maximal response averaged 13±2 nL/min in the 3-week clipped and 18±1 nL/min in the sham-operated rats ( P <.05), indicating enhanced tubuloglomerular feedback responsiveness in the nonclipped kidney. After losartan administration, mean arterial pressure decreased by 32±5 and 43±3 mm Hg, and the maximal tubuloglomerular feedback responses were markedly attenuated in both the sham-operated rats (from −12.3±1.9 to −2.4±0.9 mm Hg, P <.01) and clipped rats (from −9.6±0.6 to −1.8±0.5 mm Hg, P <.01). These data indicate that during the early stages of 2K1C Goldblatt hypertension, tubuloglomerular feedback responsiveness in the nonclipped kidney is maintained or slightly enhanced and highly dependent on Ang II type 1 receptor activation.