SYMPATHETIC NERVOUS-SYSTEM AND HYPERTENSION DURING PROLONGED TXA(2) PGH(2) RECEPTOR ACTIVATION IN RATS/

The thromboxane A(2) (TxA(2))/prostaglandin H-2 (PGH(2)) receptor mime tic U-46619 (0.6 mu g.kg(-1).min(-1)) was infused into conscious rats receiving a high-salt diet. U-46619 increased the mean arterial pressu re (MAP) over 13 days by 25 +/- 2 mmHg, whereas the MAP of vehicle-inf used controls did not change (-2 +/- 2 mmHg). In subgroups infused wit h U-46619, cardiac output was unchanged, whereas renal blood flow was reduced (before: 8.5 +/- 0.8; day 4: 5.7 +/- 0.7 ml/min; P < 0.01). If etroban (a specific TxA(2)/PGH(2) receptor antagonist) reduced MAP to basal levels in the group receiving U-46619 when infused intravenously (1-100 mu g/kg) but not intracerebroventricularly (1-100 ng/kg). Hexa methonium (10 mg/kg iv, a ganglionic blocking agent) and prazosin (0.1 mg/kg, an alpha-adrenergic antagonist) decreased MAP significantly (P < 0.05) more in the experimental group (hexamethonium, U-46619: -55 /- 3 vs. vehicle: -43 +/- 4 mmHg; and prazosin, U-46619: 28 +/- 3 vs. vehicle: 17 +/- 2 mmHg). In conclusion, hypertension during prolonged infusions of U-46619 into conscious, salt-loaded rats is accompanied b y an increase in total and renal vascular resistance and is dependent on peripheral but not central TxA(2)/PGH(2) receptors and on the auton omic and alpha(1)-adrenergic peripheral sympathetic nervous systems.