Den hemodynamiske effekt av prazosin alene og i kombinasjon med beta-blokker (tolamolol) ved essensiell hypertensjon

Summary

Several studies have shown that the cardinal haemodynamic disorder in established hypertension is an increase in the total peripheral resistance. Reduction in resistance with no or modest reduction in blood flow would seem to be a rational therapy. The purpose of this work was to study the haemodynamic long-term effects of prazosin alone and in combination with a beta-blocker in established essential hypertension. Central haemodynamic was studied at rest, supine and sitting, and during exercise at 300, 600 and 900 k.p.m. per minute. Intra-arterial blood pressure was recorded by a catheter in the brachial artery, cardiac output measured by a dye dilution method (Cardiogreen). In 10 patients treated with prazosin alone, the mean arterial pressure was reduced approximately 11% at rest and during exercise. Pressure reduction was associated with a marked decrease in the previously increased total peripheral resistance of about 17% during rest and 22% during exercise. Heart rate and cardiac output tended to be higher than before therapy, and during exercise the cardiac outputs were significantly higher than before treatment, mainly due to increase in stroke volume.

In 11 men treated with prazosin plus tolamolol the mean arterial 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 physical 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 that seen with beta-blockers alone.

One subject demonstrated a ‘first-dose reaction’ to prazosin with syncope. During the study tolamolol was withdrawn from clinical trial due to possible side-effects in long-term high dose studies in animals. After the haemodynamic study was completed, tolamolol, therefore, was replaced by timolol.

Prazosin alone or in combination with a beta-adrenoceptor blocking drug was effective in most patients with mild and moderate essential hypertension. The blood pressure reduction was mainly due to a reduction in total peripheral resistance particularly during muscular exercise. Without a beta-blocker, the blood flow was increased; with a beta-blocker there was a decrease in blood flow at rest, but no significant decrease during severe muscular exercise. It is concluded that prazosin changes the major haemodynamic disturbance in a normal direction.