Restoration of blood pressure by centrally injected U-46619, a thromboxane A(2) analog, in hemorrhaged hypotensive rats: Investigation of different brain areas

Abstract

In the present study, we investigated the cardiovascular effects of centrally injected U-46619, a thromboxane A(2) (TXA(2)) analog, and the central and peripheral mechanisms of these effects in hemorrhagic shock conditions. Hemorrhage was performed by withdrawing a total volume of 2.1 ml of blood/100 g body weight over a period of 10 min. Injections were made into the lateral cerebral ventricle (LCV), nucleus tractus solitarius (NTS), rostral ventrolateral medulla (RVLM) and paraventricular nucleus of hypothalamus (PVN). U-46619 (0.1, 1 and 2 mug) increased blood pressure and reversed hypotension in hemorrhagic shock. The pressor effect was dose- and time-dependent in all investigated brain areas. Heart rate changes were not significantly different in all groups. Pretreatment of rats with an injection of SQ-29548 ( 4 or 8 mug), a TXA(2) receptor antagonist, into the LCV, NTS, RVLM and PVN completely blocked the pressor effect of U-46619 (1 mug) injected into respective brain areas. Hemorrhage itself increased plasma adrenaline, noradrenaline, vasopressin levels and renin activity. U-46619 (1 mug) injected into the LCV, PVN, RVLM and NTS produced additional increases in these hormone levels and in renin activity. Intravenous pretreatments of rats with prazosin (0.5 mg/kg), an alpha(1)-adrenoceptor antagonist, [beta-mercapto-beta, beta-cyclopentamethylenepropionyl(1), O-Me-Tyr(2), Arg(8)]-vasopressin (10 mug/kg), a vasopressin V-1-receptor antagonist, or saralasin (250 mug/kg), an angiotensin II receptor antagonist, in hemorrhaged rats partially blocked the pressor response to U-46619 (1 mug) injected into the LCV, PVN, RVLM and NTS. Results show that centrally administered U-46619, a TXA(2) analog, increases blood pressure and reverses hypotension in hemorrhagic shock. Activation of central TXA(2) receptors mediates the pressor effect of the drug. Furthermore, the increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity are involved in these effects.