Thromboxane mediates renal hemodynamic response to infused angiotensin II.
Since we had found that angiotensin II (Ang II), but not phenylephrine (PE), increased the excretion of thromboxane (Tx) and raised mean arterial pressure (MAP) by a Tx-dependent mechanism, we tested the role of TxA2 in mediating Ang II-induced changes in renal hemodynamics. For series 1, groups of anesthetized rats received an i.v. infusion of Ang II (50 ng.kg-1.min-1). When infused with a vehicle, Ang II increased MAP, renal vascular resistance (RVR) and the excretion of TxB2 factored by GFR. A PGH2-TxA2 receptor antagonist, SQ-29,548, or three days of pretreatment with a TxA2 synthase inhibitor UK-38,485, which reduced excretion of TxB2 by 80%, blunted the rise in MAP and RVR induced by Ang II. In contrast, three days of pretreatment with indomethacin did not alter the renal vascular response to Ang II. For series 2, groups of rats received Ang II at a higher rate (500 ng.kg-1.min-1) while the RPP was stabilized at +11 to +15 mm Hg with a suprarenal aortic clamp. SQ-29,548 and UK-38,485 both prevented Ang II-induced reductions in GFR and blocked 80% of the increase in RVR. For series 3, infusions of phenylephrine at an equipressor dose to series 2 of 30 micrograms.kg-1.min-1 with control of RPP at +14 mm Hg also increased RVR but this was not blunted by SQ-29,548.


CONCLUSIONS
1.) infusion of Ang II increases excretion of filtered TxB2, causes dose-dependent increases in RVR and, at high doses, reduces GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Wilcox
C S
CS
Department of Medicine, University of Florida College of Medicine, Gainesville.
Welch
W J
WJ
Snellen
H
H
D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006439:Hemodynamics / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014655:Vascular Resistance / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D007093:Imidazoles; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D000804:Angiotensin II; C039242:dazmegrel; D013928:Thromboxane A2; C045749:SQ 29548; D013930:Thromboxane-A Synthase