Inhibition of prostaglandin synthesis by indomethacin interacts with the antihypertensive effect of atenolol.

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.

Adrenalectomy abolishes antagonism of alpha-adrenoceptor-mediated hypotension by a beta-blocker in conscious rats.

1. The effects of a single bolus injection of propranolol, atenolol or ICI 118,551, non-selective beta-, selective beta 1- and selective beta 2-adrenoceptor antagonists, respectively, on mean arterial pressure (MAP) and plasma catecholamine concentrations were examined in seven groups of conscious and unrestrained adrenalectomized rats receiving a continuous infusion of the alpha-adrenoceptor antagonist phentolamine. In all rats adrenaline was undetectable in the plasma four days after adrenalectomy. 2. In the first three groups, phentolamine significantly decreased MAP and increased the plasma concentrations of noradrenaline. The injection of propranolol, atenolol or ICI 118,551 in Groups I, II and III, respectively, caused a small increase in MAP and a small, but not significant, decrease in plasma noradrenaline concentrations. 3. Groups IV, V and VI were given a continuous infusion of adrenaline for 1 h prior to the infusion of phentolamine, followed by a bolus injection of propranolol, atenolol or ICI 118,551, respectively. Group VII was treated similarly to IV, but was also given daily cortisone replacement after adrenalectomy. Adrenaline slightly, but not significantly, decreased MAP while phentolamine significantly decreased MAP and increased plasma noradrenaline concentrations in all groups. A subsequent injection of a beta-blocker caused a significant increase in MAP in each group and a slight decrease in the plasma level of noradrenaline which reached statistical significance in group VII. The pressor effect of propranolol was significantly greater in the cortisone-treated rats (Group VII) than in Group IV. 5. The results suggest that adrenaline and adrenocortical steroids are both involved in the antagonism of alpha-adrenoceptor-induced hypotension by a beta-blocker.

Atenolol oral en el manejo del hemangioma infantil: serie de casos de 46 pacientes / Oral Atenolol for Infantile Hemangioma: Case Series of 46 Infants

El propranolol, un betabloqueante no selectivo, sigue siendo la primera línea de tratamiento para el hemangioma infantil problemático. Sin embargo, aunque poco frecuente, un subgrupo de pacientes experimenta efectos secundarios indeseables, lo que despierta el interés sobre otros betabloqueantes selectivos. Presentamos una amplia serie de casos de 46 lactantes tratados con éxito con atenolol, un bloqueante selectivo beta-1

Propranolol, a non-selective beta-blocker, remains the first line of treatment for problematic infantile hemangioma. However, although rarely, a subset of patients experience undesirable side effects, raising interest in other selective beta-blockers. We present a large case series of 46 infants treated successfully with oral atenolol, a selective beta-1 blocker

Naloxone pretreatment blocks the hypotensive effects of atenolol in SHR and WKY rats.

The present study examined the interaction of opioidergic systems in the hypotensive action of atenolol. Anesthetized, adult spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were instrumented to monitor blood pressure and heart rate. Atenolol (100 micrograms/kg, i.v.) produced a decrease in blood pressure of similar magnitude in both SHR and WKY rats. However, the bradycardia was greater in SHR. Pretreatment with naloxone (0.1 mg/kg, i.v.) 15 min prior to the administration of atenolol completely prevented the hypotensive response in SHR and decreased the maximum hypotensive response by approximately 50% in WKY rats. The atenolol-induced bradycardia was unaffected in both groups of animals. Additionally, pretreatment with yohimbine, an alpha 2-receptor antagonist, inhibited the hypotensive response of atenolol in SHR. Collectively, these results suggest an interaction between opioidergic and catecholaminergic systems as a possible site of action of antihypertensive drugs.

The interference of indomethacin and of imidazole salicylate on blood pressure control of essential hypertensive patients treated with atenolol. Preliminary report.

To evaluate whether imidazole salicylate, a recently developed NSAID, can interfere with the antihypertensive effect of atenolol and to compare its action with that of indomethacin, 9 essential hypertensives, while on prolonged (more than 1 month) treatment with atenolol (100 mg qd) received, according to a double-blind cross-over study, imidazole salicylate (750 mg t.i.d.) or indomethacin (50 mg b.i.d. plus a placebo tablet) for 1 week, reverting the treatment after a 2-week wash-out period. While indomethacin addition significantly increased blood pressure, when compared to atenolol alone, imidazole salicylate did not change it. These data show that imidazole salicylate, unlike indomethacin, does not reduce the antihypertensive effect of atenolol.

Flurbiprofen interaction with single doses of atenolol and propranolol.

In patients with mild hypertension, flurbiprofen in a dose of 100 mg daily for 7 days attenuated the hypotensive effect of a single dose of propranolol 80 mg but not of atenolol 100 mg. The attenuation was not due to an effect on the pharmacokinetic profile of either propranolol or atenolol. An alternative explanation is required.