Molsidomine, a new long-acting vasodilator, was administered intravenously (0.03 mg per kilogram of body weight) to two groups of six patients with stable anginapectoris. In the first group, studied during exercise-induced angina, the drug shortened the duration of pain and reduced electrocardiographically measured ST-segment depression, mean systemic arterial pressure, and mean pulmonary wedge pressure. Cardiac output and heart rate remained unchanged. In the second group, studied during pacing-induced angina, the drug reduced both left ventricular pressures and angiographically estimated ventricular volumes and improved the ejection fraction. In a double-blind crossover comparison with a placebo, molsidomine (2 mg three times daily) reduced the frequency of anginal attacks and the consumption of nitroglycerin tablets in 14 patients. During exercise testing on a treadmill a statistically significant reduction in ST-segment depression lasted for up to six hours. These studies suggest that molsidomine acts like nitroglycerin but its effects last longer. We conclude that molsidomine is effective in preventing the symptoms of angina pectoris. (N Engl J Med 302:1-6, 1980).
The effects of single and combined selective blockade of the sympathetic alpha-and beta-receptors were examined in patients with severe hypertension (diastolic pressure > I20 mmHg) uncomplicated by cardiac or renal failure. Given In uncomplicated essential hypertension the raised blood pressure is accompanied by a normal cardiac output (Taylor, Donald, and Bishop, I957). The increased peripheral resistance is uniformly distributed throughout all the regional circulations and resides predominantly in the peripheral arterioles (Freis, I960). These vessels regulate the resistance in many of the regional vascular beds, and particularly in the kidney, through sympathetic alphaadrenergic receptors (Moran, I966).Thus it is reasonable to expect that drugs which possess both vasodilator properties and also the ability to inhibit stimulation of the adrenergic alpha-receptors may offer substantial advantages over other less specific agents in the treatment of hypertensive vascular disease. Phentolanine, an alpha-receptor antagonist with conspicuous vasodilator properties (Taylor et al., i965a, b; Majid, Sharma, and Taylor, 197i), has been shown to be effective in acutely lowering the blood pressure of hypertensive patients (Taylor et al., i965a I965a; Majid et al., 197I). For this reason it is logical to combine drugs that block both the alphaand beta-adrenoreceptors so that the reflex increase in sympathetic stimulation of the heart that occurs in response to the fall in blood pressure induced by alpha-receptor blockade is prevented by inhibition of the cardiac beta-receptors.The following investigation was, therefore, undertaken to test this thesis by acute haemodynamic studies in patients with severe hypertensive disease and to determine the clinical effectiveness of the combination of oral alpha-and beta-receptor antagonists in the longer term treatment of these patients.Patients and methodsTwelve patients with severe uncomplicated essential hypertension were studied. Five were men, average age 47 years (range 44 to 50 years) and average weight 89 kg (range 84 to 98 kg); 7 were women average age 41 years (range 34 tO 49 years) and average weight 60 kg (range 49 to 83 kg). Seven patients presented with severe headaches which had proved intractable to other antihypertensive drugs, singly or in combination. In the remainder a high blood pressure was discovered during routine medical examination for minor illnesses. The lowest diastolic pressure measured in the supine position by doctors in the ward persistently exceeded I20 mmHg (range I20 to I50) in all patients during their hospital on 12 May 2018 by guest. Protected by copyright.
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