Feedback responses during sequential inhibition of angiotensin and thromboxane.
Since thromboxane (Tx) can mediate the actions of angiotensin II (ANG II), we investigated interaction between these systems on the tubuloglomerular feedback (TGF) response. TGF was assessed from proximal stop-flow pressure (PSF) during orthograde perfusion of the loop of Henle (LH) between 0 and 40 nl/min. In the basal state, TGF was 11.3 +/- 0.8 mmHg. In series 1 experiments, it was unaltered by vehicle (+0.3 +/- 0.9 mmHg, n = 9, NS), was reduced by an ANG II antagonist, saralasin (-2.4 +/- 1.1 mmHg, n = 8, P less than 0.0005), and by a TxA2 antagonist SQ 29,548 (-4.8 +/- 0.6 mmHg, n = 11, P less than 0.0001). Both drugs together produced an additive blunting of TGF of -6.9 +/- 0.7 mmHg. In series 2 experiments, TGF was again unchanged by vehicle (+0.2 +/- 0.6 mmHg). It was reduced by -4.4 +/- 0.2 mmHg (P less than 0.0001) by an angiotensin-converting enzyme inhibitor CGS-14,824A (50 mg/kg, n = 5) and by -4.0 +/- 0.4 mmHg (P less than 0.001) by a Tx synthesis inhibitor CGS-13,080 (50 mg/kg, n = 7). Although both drugs together produced a further blunting of the response of -6.1 +/- 0.4 mmHg, this was significantly (P less than 0.001) less than additive. In both series, a response (averaging 3.5 +/- 0.3 mmHg) persisted in all rats given combined antagonists or inhibitors. In conclusion, both ANG II and TxA2 can modulate TGF-induced changes in PSF independently, and the response probably requires other system(s) in addition to ANG II and TxA2.
Welch
W J
WJ
Department of Medicine, College of Medicine, University of Florida, Gainesville.
Wilcox
C S
CS
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D005246:Feedback; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D010865:Pilot Projects; D051381:Rats; D011919:Rats, Inbred Strains; D012504:Saralasin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D000804:Angiotensin II; D013928:Thromboxane A2; C045749:SQ 29548; D013930:Thromboxane-A Synthase; D012504:Saralasin