Antihypertensive effect of thromboxane A2 receptor blockade in genetically hypertensive rats of the Lyon strain.
In order to determine whether the increased renal biosynthesis of thromboxane A2, observed in young genetically hypertensive (LH) rats of the Lyon strain, could be involved in the development of their hypertension, 12 LH female rats were given a specific thromboxane A2 receptor antagonist, AH 23848 (Glaxo Group Research) orally (2 mg/kg twice a day) from 3 to 9 weeks of age. In addition, 12 LH and 12 normotensive (LN) rats were given vehicle only (sodium bicarbonate 8%). The thromboxane receptor antagonist AH 23848, which inhibited platelet aggregation by about 65%, did not modify the renal production of thromboxane A2, prostaglandin I2 (PGI2) or prostaglandin E2 (PGE2). It induced a progressive, potent and long lasting decrease in systolic blood pressure which was normalized in 6-, 7- and 8-week-old LH rats, thus demonstrating the involvement of thromboxane A2 in the onset of hypertension in this model. In contrast with thromboxane synthetase inhibitors, the AH 23848 antihypertensive effect persisted 1 week after the cessation of treatment, showing the superiority of thromboxane A2 receptor blockade over thromboxane synthetase inhibition.
Geoffroy
J
J
Department of Physiology and Clinical Pharmacology, UA CNRS 606, Faculty of Pharmacy, Lyon, France.
Benzoni
D
D
Sassard
J
J
D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003864:Depression, Chemical; D004353:Drug Evaluation, Preclinical; D005260:Female; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011982:Receptors, Prostaglandin / Q000187:drug effects* / Q000502:physiology; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D001713:Biphenyl Compounds; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; C046926:AH 23848