title: Feedback responses during sequential inhibition of angiotensin and thromboxane.
abstract: 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.
authors.affiliation: Department of Medicine, College of Medicine, University of Florida, Gainesville.
authors.forename: W J
authors.initials: WJ
authors.lastname: Welch
authors.forename: C S
authors.initials: CS
authors.lastname: Wilcox
mesh_terms: 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
chemical_list: 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