Chronic haemodynamic effects of carvedilol in essential hypertension at rest and during exercise

Nineteen men (mean age 44 years) with essential hypertension, WHO stage I, were studied invasively at rest and during exercise. Blood pressure was recorded intra-arterially (brachial artery), cardiac output by dye dilution method and heart rate by electrocardiography. After initial pre-drug recordings, the patients received 25 mg carvedilol orally and central haemodynamics at rest and during exercise were recorded 1 and 2 h after tablet intake to evaluate the immediate effects of carvedilol. The results indicated a combined beta-blocking and vasodilating effect. After 6-9 months of treatment, supine haemodynamics were recorded 12-24 h after the last dose and then 1 and 2 h after an additional 25 mg dose. During chronic treatment (2 h after last dose at rest supine) mean arterial pressure was reduced by 17% (P less than 0.001) and total peripheral resistance index by 6% (NS) while heart rate and cardiac index were reduced by 12%. Exercise haemodynamics demonstrated a fall in blood pressure of 17% (P less than 0.001). Exercise stroke index increased by 5% (NS), partly compensating for the reduction in heart rate of 17%. Total peripheral resistance index was reduced by 5% (NS). It is concluded that carvedilol is an effective anti-hypertensive agent in a large proportion of patients with essential hypertension. The haemodynamic mode of action reflects an alpha 1-blocking activity, particularly in situations with low sympathetic tone. During exercise the beta 1-blocking activity (demonstrated by the reduction in heart rate) is more prominent.