Sixteen patients with mild to moderate essential hypetension were treated with cardioselective beta-blocker (atenolol or metoprolol). Atenolol, 50 mg once daily, was given for 4-12 weeks to 9 patients (Group A, mean age 66.2 years) and metoprolol, 20 mg three times daily, for 12 weeks to 7 patients (Group M, mean age 70.7 years). Hemodynamic measurements, which were obtained before and 5 min after intravenous infusion of isoproterenol (ISP) (0.02μg/kg/min), were performed in all subjects before and after the treatment with oral cardioselective beta-blocker therapy.
In Group A, systolic blood pressure (SBP) and diastolic blood pressure (DBP) fell significantly (p<0.025), SBP: 171±5.7 to 159±6.3 mmHg, DBP: 99±3.8 to 90±5.2 mmHg. In Group M, SBP tended to fall but DBP was unchanged. Heart rate (HR) decreased in Group A (74±4.7 to 57±2.8/min, p<0.005) more than in Group M (69±5.0 to 62±4.5/min, p<0.05). Cardiac index (CI) was unchanged in Group A, but decreased significantly in Group M (3.36±0.27 to 2.78±0.28 l/min/M2, p<0.005). Stroke index, mean transit time incresaed in Group A, but were unchanged in Group M. Systemic vascular resistance, peripheral venous pressure, total blood volume were unchanged in both Group A and Group M.
In response to ISP stimulation, increasing rate of HR was +49.9% and +35.8% before and after the treatment in Group A, respectively. Heart rate increased by +48.9% and +44.3% before and after the treatment in Group M, respectively. Increasing rate of CI was +71.5% and +30.8% before and after the treatment in Group A, respectively. CI increased by +52.5% and +48.4% before and after the treatment in Group M. Therefore, beta-blocking effects on HR and CI to ISP stimulation were not observed in both Group A and Group M as compared with those to ISP stimulation after the treatment with non-cardioselective beta-blocker (oxprenolol) that we observed previously. In oxprenolol therapy, increasing rate of HR was +44.3% and +13.2% before and after the treatment, and that of CI was +52.4% and +1.1% before and after the treatment. Intravenous atropine did not alter the response to ISP after the treatment of atenolol suggesting that the reflex vagal control was not involved in this response.
It was concluded that oral cardioselective beta-blocker therapy in essential hypertension was effective in reduction of blood pressure and HR, but showed no beta-blocking to ISP stimulation. This unexpected response is not attributed to reflex vagal suppression due to stilmulation of vascular beta-2 receptor by ISP, but may reveal the direct stimulation of cardiac beta-2 receptor by ISP.