We tested the hypothesis that baroreflex attenuation during sodium depletion is due to increased prostaglandin (PG) levels. We studied baroreflex sensitivity before and after PG synthesis inhibition in conscious cynomolgus monkeys. Arterial pressure and pulse interval (PI) were measured during intravenous infusions of phenylephrine (1-20 micrograms.kg-1.min-1, n = 6) and nitroprusside (1-10 micrograms.kg-1.min-1, n = 7). Infusions were repeated 30 min after indomethacin (Indo, 6 mg/kg iv). The slope (in ms/mmHg) of the mean arterial blood pressure-PI plot was used as an index of baroreflex sensitivity. Plasma renin activity (PRA) was elevated (47.9 +/- 9.7 vs. 8.8 +/- 3.3 ng angiotensin I.ml-1.h-1) after sodium depletion (P < 0.05). Baroreflex sensitivity to hypotension and hypertension was significantly (P < 0.05) attenuated by sodium depletion (3.69 +/- 0.9 vs. 0.9 +/- 0.1 ms/mmHg and 7.38 +/- 0.6 vs. 5.04 +/- 0.9 ms/mmHg, respectively). Indo decreased PRA to 28.6 +/- 5.7 ng angiotensin I.ml-1.h-1 (P < 0.05) in sodium-depleted monkeys and decreased heart rate -21 +/- 3.7 from a baseline of 166 +/- 9.40 beats/min in normal monkeys and -22 +/- 2.9 from a baseline of 191 +/- 7.9 beats/min in low-sodium monkeys (P < 0.05). Indo did not significantly change baroreflex sensitivity in either group. Thus the baroreflex was attenuated in conscious nonhuman primates during sodium depletion; acute PG synthesis blockade did not improve baroreflex sensitivity. Indo decreased heart rate without changing arterial pressure; suggesting that PGs caused a downward resetting of the pressure-heart rate relationship.

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1 Nineteen patients receiving oxprenolol slow-release (SR) 160 mg (three patients) or 320 mg (16 patients) once daily for mild to moderate hypertension were treated with oxprenolol Oros 16/260 once daily for 3 weeks following a 2 week placebo wash-out period. 2 Repeated dosing with both Oros and SR oxprenolol preparations, in comparison with placebo, significantly reduced supine systolic and diastolic blood pressures, and pulse rate at 24 h after dosing. Single Oros doses also significantly reduced pulse rate and diastolic, but not systolic, blood pressure at 24 h. The reduction in supine systolic blood pressure was greater during repeated dosing with oxprenolol SR than after a single dose of the Oros preparation. 3 Control of supine diastolic blood pressure (-90 mm Hg) at 24 h after dosing was achieved in 13 out of 18 patients with oxprenolol SR (two out of three patients given 160 mg, and 11 out of 15 given 320 mg). Similar control was achieved in 11 out of 18 patients after a single dose of oxprenolol Oros, and in 13 out of 17 patients treated for 3 weeks. 4 The mean percentage reduction in exercise heart rate (EHR) compared to placebo, at 24 h after dosing, was 16% following Oros treatment for 3 weeks, and 12% following SR administration. After a single dose of oxprenolol Oros EHR, was reduced by 9% at 24 h compared to placebo. At 3 weeks the Oros formulation was significantly better than the SR tablet at reducing EHR. 5 Oxprenolol Oros 16/260 was effective over 24 h and well tolerated. Once daily administration with this dosage form represents a useful treatment for mild to moderate hypertension.

Background and Aims-There is growing evidence that bile acids are involved in the regulation of triglyceride-, cholesterol-homeostasis and fat absorption. In this study organ-specific Fxr knockout mice were used to further investigate the influence of FXR in lipogenesis.

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