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The interaction of inhibition of prostaglandin (PG) synthesis by indomethacin (75 mg/day) with the antihypertensive effect of atenolol (50 mg b.i.d.) was studied in 11 untreated otherwise healthy men 35 to 45 years old with essential hypertension. Atenolol for 3 weeks decreased supine blood pressure (BP) from 157/109 mm Hg during placebo to 148/97 mm Hg. Indomethacin alone for 1 week slightly increased BP and antagonized the antihypertensive action of atenolol. Atenolol reduced plasma renin activity (PRA) to 40% but did not modify either the urinary excretion of vasodilatory PGs (PGE2 and prostacyclin measured as 6-keto-PGF1 alpha) or plasma kininogen and urine kallikrein. Indomethacin suppressed PRA to 27% and PG excretion to approximately 70% but did not markedly change plasma kininogen and urine kallikrein excretion. The decreased excretion of 6-keto-PGF1 alpha, the metabolite of the main vasodilatory prostanoid prostacyclin, correlated with the increased BP measured in standing subjects. The effects of indomethacin were practically the same when given with atenolol as when given alone. We conclude that the slight increase in BP by indomethacin in essential hypertension is associated with the reduced production of vasodilatory PGs but not with alterations in activities of the renin-angiotensin or kallikrein-kinin systems.

Renal denervation delays the development of hypertension in spontaneously hypertensive (SH) rats. The influence of bilateral surgical renal sympathectomy, verified by fluorescence microscopy, on blood pressure and plasma renin activity in SH and normotensive rats (170-180 g before the sympathectomy) was studied. Neither in SH nor in normotensive rats, did the preoperative systolic blood pressure in the renal-sympathectomized group differ from that in the sham-operated controls. After the sympathectomy, blood pressure in the SH rats increased in 4 weeks only insignificantly, from 160 +/- 3 to 172 +/- 6 mmHg, while that in the sham-operated SH rats rose from 163 +/- 5 to 191 +/- 5 mmHg. In normotensive rats, blood pressures in both the renal-sympathectomized and sham-operated groups remained at the pre-operative levels. Thirty days after the operations, plasma renin activity or plasma kininogen in the renal-sympathectomized group did not differ from that in the sham-operated one either in SH or in normotensive rats. The results suggest that the delay in hypertension development produced by renal sympathectomy in SH rats is not mediated by a reduction in renin secretion.

The present study compares the clinical efficacy and side-effects of amoxycillin in two groups of children at the age of six years or less randomly assigned to amoxycillin therapy 40 mg/kg/day either two or three times daily for the clinical diagnosis of acute respiratory tract infections. Both treatment groups were comparable according to age, sex, weight and additional treatment. Acute otitis media occurred in 152 out of 187 (81%) patients receiving amoxycillin three times daily, and in 153 out of 180 (85%) patients with a twice daily dosage schedule. A clinical diagnosis of acute bronchitis was made in 55 cases (29%) in the former group and in 59 cases (33%) in the latter group. In the patient group with twice daily dosage schedule, 82% of the patients with otitis media were cured. The corresponding figure in the thrice daily group was 86%. On the basis of the disappearance of the symptoms and the improvement of the signs the overall results are equally good in both treatment groups. The number of side-effects of amoxycillin was equal in both groups, 6.4% and 6.7% respectively. Exanthem was the most frequent side-effect. No serious side-effects occurred. Our results indicate that the same total daily dose of amoxycillin given either three times daily or two times daily is comparably effective and tolerated in children with acute respiratory infections, e.g. acute otitis media and acute bronchitis.

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