Chloride channel blockade attenuates the effect of angiotensin II on tubuloglomerular feedback in WKY but not spontaneously hypertensive rats.
Recent studies have shown that calcium-dependent chloride channels may play a crucial role in the modulation of the vascular effects of angiotensin II (ANG II). Thus, alterations in the function of these channels may be responsible for the enhanced renal vasoconstrictor and tubuloglomerular feedback (TGF) response to ANG II in spontaneously hypertensive rats (SHR). We investigated the effect of the calcium-dependent chloride channel blocker IAA-94 on renal hemodynamics and TGF responses. The renal interstitium was perfused with control solution, with ANG II, and with both ANG II and IAA-94. In Wistar Kyoto rats (WKY), perfusion with ANG II significantly increased renal vascular resistance (RVR), but the effect was significantly attenuated by perfusion with ANG II/IAA-94. In SHR, ANG II caused a significant elevation of RVR that was not altered by the simultaneous infusion of IAA-94. Proximal tubular stop flow pressure (P(sf)) was monitored during perfusion of peritubular capillaries with control solution, and subsequently with IAA-94, ANG II or both ANG II and IAA-94. TGF response magnitude of WKY rats was significantly augmented with ANG II, and this effect was suppressed by perfusion with ANG II /IAA-94. However, in SHR peritubular perfusion with ANG II/IAA-94 did not suppress the TGF response. We conclude that chloride channels susceptible to IAA-94 may play a significant role in modulating the effects of ANG II on renal hemodynamics, and that this modulation is absent in SHR.
Hashimoto
Seiji
S
Department of Internal Medicine II, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan. Seijih@intra.niddk.nih.gov
Kawata
Tetsuya
T
Schnermann
Jurgen
J
Koike
Takao
T
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D005246:Feedback; D006016:Glycolates / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology*; D008297:Male; D011677:Punctures; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D018118:Chloride Channels; D006016:Glycolates; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C015765:MK 473