Haemodynamic long-term effects of prazosin plus tolamolol in essential hypertension.

Twelve men with untreated essential hypertension in WHO stage I were studied on an outpatient basis to evaluate the haemodynamic long-term effects of a combination of prazosin and a β-adrenoceptor blocker, tolamolol. Oxygen consumption, heart rate, cardiac output (Cardiogreen) and intra-arterial brachial pressure were recorded at rest in a supine and sitting position and during steady state work at 300, 600 and 900 kpm/min. The subjects were treated with the combination of prazosin (dose 3-6 mg daily) plus tolamolol (150-300 mg daily) for 7-12 months and the haemodynamic study was repeated. The blood pressure was reduced approximately 18% at rest and during exercise. The pressure reduction was due to a combination of reduction in cardiac index and total peripheral resistance. During hard exercise the cardiac index was almost unchanged, the pressure reduction being almost entirely due to reduction in total peripheral resistance. The heart rate was reduced significantly, but less than what is seen by β-adrenoceptor-blockers alone. One subject demonstrated the `first dose reaction' of prazosin with syncope. During the study tolamolol was withdrawn from clinical trials due to possible side-effects in long-term high dose studies in animals. After the haemodynamic study was completed, tolamolol was replaced by timolol without changes in the blood pressure. The combination of prazosin and a β-adrenoceptor blocking drug is very effective in most patients with mild and moderate essential hypertension. The blood pressure reduction is due to a combination of reduction in total peripheral resistance and in cardiac index, the latter being only slightly decreased during severe muscular exercise.