MODULATION OF TUBULOGLOMERULAR FEEDBACK BY ANGIOTENSIN-II TYPE-1 RECEPTORS DURING THE DEVELOPMENT OF GOLDBLATT HYPERTENSION

It has been suggested that the increased levels of angiotensin II (Ang II) in the contralateral kidney of two-kidney, one clip (2K1C) Goldbl att hypertensive rats act to enhance tubuloglomerular feedback respons iveness and proximal tubular reabsorption and thereby exert a substant ial sodium-retaining influence on the nonclipped kidney. The current s tudy investigated the Ang II dependency of tubuloglomerular feedback r esponsiveness in the nonciipped kidney during the early stages of deve lopment of 2K1C hypertension. Stop-flow pressure feedback responses we re assessed in the nonclipped kidney of 2K1C rats during control condi tions and after systemic administration of the Ang II type 1 receptor antagonist losartan (10 mg/kg). In 1-week clipped and shamoperated rat s, 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 re sponses (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 shama operated a nd 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 re sponses were similar in 3-week clipped and sham-operated rats, the lat e proximal perfusion rate eliciting a half-maximal response aver aged 13+/-2 nL/min in the 3-week clipped and 18+/-1 nL/min in the sham-oper ated rats (P<.05), indicating enhanced tubuloglomerular feedback respo nsiveness in the nonclipped kidney. After losartan administration, mea n arterial pressure decreased by 32+/+5 and 43+/-3 mm Hg, and the maxi mal tubuloglomerular feedback responses were markedly attenuated in bo th 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 hyperten sion, tubuloglomerular feedback responsiveness in the nonclipped kidne y is maintained or slightly enhanced and highly dependent on Ang II ty pe 1 receptor activation.