Attenuation of the development of hypertension in spontaneously hypertensive rats by the thromboxane synthetase inhibitor, 4'-(imidazol-1-yl) acetophenone.
The compound 4'-(imidazol-1-yl) acetophenone was demonstrated to be a selective thromboxane (Tx) synthetase inhibitor in spontaneously hypertensive rats (SHR). Serum TxB2 concentrations (from clotted blood) were suppressed by 89.1% (p less than 0.001) and 41.2% (p less than 0.01) at 3 and 24 hours, respectively, following a single subcutaneous injection of 100 mg/kg of 4'-(Imidazol-1-yl) acetophenone suspended in olive oil. In contrast, plasma 6-keto-PGF1 alpha levels were not significantly altered at 3 hours following injection - a time when suppression of TXB2 was maximal. From 4 to 10 weeks of age, SHR were treated with daily injections of either 4'-(Imidazol-1-yl) acetophenone (100 mg/kg) in olive oil or olive oil alone. By 8 weeks of age systolic blood pressures in the treated group were 140.6 +/- 3.2 vs 156.6 +/- 4.5 mmHg in the control group (p less than 0.01). At ten weeks of age the separation was even more pronounced: 155.3 +/- 3.7 vs. 184.8 +/- 4.6 mmHg for treated vs. control animals (p less than 0.001). This data supports the hypothesis that thromboxanes may be involved in the development of SHR hypertension; however, alternative mechanisms are discussed.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D006973:Hypertension / Q000235:genetics / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007700:Kinetics; D051381:Rats; D013929:Thromboxane B2 / Q000097:blood*; D013931:Thromboxanes / Q000097:blood*
D007093:Imidazoles; D013931:Thromboxanes; C034480:Ro 22-3581; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha