Contrasting effect of thromboxane synthase inhibitors and a thromboxane receptor antagonist on the development of angiotensin II-salt-induced hypertension in rats.
This study was designed to contrast the effects of prolonged treatment with a thromboxane (Tx) synthase inhibitor (UK 38485 or SC 41156) and a Tx receptor antagonist (SQ 29548) on the development of angiotensin II (Ang II)-salt-induced hypertension. Ang II infusion (125 ng/min i.p. for 12 days) in rats drinking 0.15 M NaCl resulted in severe hypertension accompanied by proteinuria, reduction of urinary creatinine excretion and augmentation of urinary TxB2 excretion and TxB2 release from aortic rings and renal cortex slices. In saline-drinking rats undergoing Ang II infusion, the concomitant administration by gavage of UK 38485 (100 mg/kg/day) or SC 41156 (25 mg/kg/day) reduced serum and urinary TxB2 and TxB2 release from aortic rings and/or renal cortex slices, but it was without effect on the development of hypertension. In contrast, concomitant infusion of SQ 29548 (4.2 mg/24 hr s.c.) significantly attenuated the increase of blood pressure produced by the infusion of Ang II in saline-drinking rats. This effect of SQ 29548 may be the consequence of blockade of the actions of one or more endogenous eicosanoids that increase blood pressure by a mechanism(s) involving interaction with TxA2 receptors. This implies that pressor eicosanoids play a contributory role in the development of severe Ang II-salt hypertension.
Mistry
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Department of Pharmacology, University of Tennessee, Memphis.
Nasjletti
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A
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D012965:Sodium Chloride / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D007093:Imidazoles; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D000804:Angiotensin II; C039242:dazmegrel; D012965:Sodium Chloride; D013928:Thromboxane A2; C045749:SQ 29548; D013930:Thromboxane-A Synthase